Showing papers in "Immunopharmacology and Immunotoxicology in 2006"
TL;DR: Methanolic extract of Andrographis paniculata was found to inhibit formation of oxygen derived free radicals such as superoxide, hydroxyl radicals, lipid peroxidation and nitric oxide in in vitro system and in vivo studies.
Abstract: In this study, we explored the antioxidant and anti-inflammatory properties of the medicinal herb Andrographis paniculata using in vitro as well as in vivo systems. Methanolic extract of Andrographis paniculata was found to inhibit formation of oxygen derived free radicals such as superoxide (32%) hydroxyl radicals (80%) lipid peroxidation (80%) and nitric oxide (42.8%) in in vitro system. In vivo studies using BALB/c mice models also showed significant inhibition in PMA induced superoxide (32.4%) and nitric oxide (65.3%) formation. Interestingly we also found that, administration of Andrographis paniculata extract produced complete inhibition of carageenan induced inflammation compared with control models.
159 citations
TL;DR: Data indicate that phytoncides significantly enhance human NK activity and this effect is at least partially mediated by induction of intracellular perforin, granzyme A, and granulysin.
Abstract: To explore the effect of forest bathing on the human immune system, we investigated the effect of phytoncides (wood essential oils) on natural killer (NK) activity and the expression of perforin, g...
146 citations
TL;DR: A number of ligands acting as exogenous or host-derived agonists for FPRs, as well as ligand acting as FPRS antagonists, have been described, indicating that these receptors may be differentially modulated by distinct molecules.
Abstract: Ligation of N-formyl-methionyl-leucyl-phenylalanine (fMLP) to its specific cell surface receptors triggers different cascades of biochemical events, eventually leading to cellular activation. The formyl peptide receptors (FPRs) are members of the seven-transmembrane, G-protein coupled receptors superfamily, expressed at high levels on polymorphonuclear and mononuclear phagocytes. The main responses elicited upon ligation of formylated peptides, referred to as cellular activation, are those of morphological polarization, locomotion, production of reactive-oxygen species and release of proteolytic enzymes. FPRs have in recent years been shown to be expressed also in several non myelocytic populations, suggesting other unidentified functions for this receptor family, independent of the inflammatory response. Finally, a number of ligands acting as exogenous or host-derived agonists for FPRs, as well as ligands acting as FPRs antagonists, have been described, indicating that these receptors may be differentially modulated by distinct molecules.
78 citations
TL;DR: The nonhepatotoxic nature of NLP was proved and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment, as histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of N LP.
Abstract: Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).
63 citations
TL;DR: It is suggested that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB through aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.
Abstract: Modulation of immune response to alleviate diseases has long since been of interest. Plant extracts have been widely investigated for their possible immunomodulatory properties. We have evaluated the immunomodulatory activity of aqueous extract of Rhodiola rhizome in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage cell line RAW 264.7. The Rhodiola extract was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human PBMCs as well as RAW 264.7 cell line. It also increased production of nitric oxide synergistically in combination with lipopolysaccharide (LPS) in RAW 264.7. Rhodiola at 250 microg/ml increased the p-IkappaB expression in human PBMCs. Aqueous extract of Rhodiola (250 microg/ml) also activated the nuclear translocation of NF-kappaB in human PBMCs, which is comparable to the positive stimulant LPS. Thus, our present study suggests that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB. Our study demonstrates immunostimulatory potential of aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.
59 citations
TL;DR: Oral administration of SAA attenuates asthmatic manifestations including AHR and airway inflammation, which possibly result from selective inhibition of Th2 response to allergen, and suggests that SAA may be effectively applied to control other Th2-related diseases as well as allergic asthma.
Abstract: Semen armeniacae amarum (SAA) has long been used to control asthma in Korean traditional medicine. However, its antiasthmatic action still remains poorly understood. In the current study, effective mechanism of SAA was investigated in a mouse model of allergic asthma induced by repeated sensitization and intranasal challenge with OVA. Airway hyperreactivity (AHR) measured by beta-methacholine-induced airflow obstruction and airway recruitment of leukocytes including eosinophils were significantly reduced by oral treatment of SAA water extract. Level of interleukin (IL)-4, but not Interferon gamma (IFN-gamma), in the bronchoalveolar lavage fluid (BALF) also appeared considerably lower in SAA-treated mice than in controls. Collectively, these data show that SAA suppresses type 2 helper T cell (Th2), but not type 1 helper T cell (Th1), response. This hypothesis was supported further by the data of ex vivo cytokine production of peribronchial lymph node cells. Thus, oral administration of SAA attenuates asthmatic manifestations including AHR and airway inflammation, which possibly result from selective inhibition of Th2 response to allergen. Our data strongly suggest that SAA may be effectively applied to control other Th2-related diseases as well as allergic asthma.
51 citations
TL;DR: The therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate) is revealed and may recommend it as a second-line drug in the treatment of rheumatic arthritis.
Abstract: This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.
45 citations
TL;DR: Sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.
Abstract: Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-gamma in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.
39 citations
TL;DR: The effect of Thuja occidentalis extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice and a remarkable reduction in tumor-nodule formation was shown.
Abstract: The effect of Thuja occidentalis extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. The extract was administered by three different modalities. A remarkable reduction in tumor-nodule formation was shown by simultaneous (74.4%) and prophylactic (71.5%) mode of administration. The effect was comparatively low in drug administration after tumor development (60.2%). Increased lung collagen hydroxyproline (21.13 µg/mg protein) in the metastasized lungs of control animals compared with normal animals (0.98 µg/mg protein) was significantly reduced in Thuja-treated animals. The elevated level of uronic acid (349.5 µg/100 mg tissue) and hexosamine contents in metastatic control animals was significantly reduced in the animals treated with alcoholic extract of Thuja. Similarly the elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with the extr...
36 citations
TL;DR: Short-term oral administration of ginseng extract appears to enhance Th1-type cytokine production, which is a major ingredient in tonic recipes in eastern Asian countries.
Abstract: Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine used as a major ingredient in tonic recipes in eastern Asian countries. In our study, male BALB/c mice were treated orally with various doses of ginseng root extract for 5 consecutive days. The extract reduced the serum level of IgG but elevated the level of IgA. Under in vitro condition, the lipopolysaccharide-stimulated spleen cells from the ginseng-treated mice also showed a significant decrease in IgG production but an increase in IgA production. The serum level and production of IgM was unaffected. The interleukin-2, interferon-gamma (Th1-type cytokines), and interleukin-10 (Tr1-type cytokine) production by Con A-stimulated spleen cells from the ginseng-treated mice showed an upregulation relative to the control group. However, the production of interleukin-4 (Th2-type cytokine) showed no significant change. The activity of natural killer cells was increased in the ginseng group, but the percentages of T-lymphocytes (CD3(+)) and CD4(+)8(-), CD4(-)8(+) subset were reduced. Thus, short-term oral administration of ginseng extract appears to enhance Th1-type cytokine production.
29 citations
TL;DR: It is suggested that interleukin-6 plays a critical role in airway inflammatory responses induced by diesel exhaust inhalation.
Abstract: To clarify the possible role of interleukin-6 in aggravation of inflammatory responses in diesel exhaust-exposed mice, we compared the infiltration of inflammatory cells and the production of chemokines between interleukin-6-deficient and wild-type mice following 0, 1.0, or 3.0 mg diesel particles/m3 diesel exhaust inhalation for 4 weeks. Exposure to diesel exhaust significantly increased the number of inflammatory cells and the amount of CCL17 and CXCL3 in bronchoalveolar lavage fluids from wild-type mice, but not in interleukin-6-deficient mice. These findings suggest that interleukin-6 plays a critical role in airway inflammatory responses induced by diesel exhaust inhalation.
TL;DR: Evidence is provided that AIAE may be beneficial in the treatment of allergic diseases as it dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.
Abstract: The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.
TL;DR: Bronchoalveolar lavage data indicated that the Th1/Th2 balance of CD4+ T cells in the BAL differs between active IPF and CVD, even though KL-6 is elevated in both diseases.
Abstract: The balance between CD4(+) T helper (Th1) lymphocytes producing interferon-gamma or Interleukin-4 (Th2) in the lungs may vary among diseases and during the progression of interstitial pneumonia (IP). Both idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (CVD) are associated with IP, but the clinical course and the response to treatment are different. Since Th1 or Th2 modulating drugs have been proven to alter the lymphocyte balance in vitro, it is important to elucidate the Th1/Th2 profile in patients with active IP. Bronchoalveolar lavage (BAL) was performed in patients who had IPF (n = 12) or CVD (n = 12) with IP, as well as in patients who had bronchoectasis and bronchopneumonia (n = 12). The CVD patients had rheumatoid arthritis (n = 6), Sjogren's syndrome (n = 2), dermatomyositis (n = 1), progressive systemic sclerosis (n = 2), and CREST syndrome (n = 1) as the underlying diseases. IP activity was evaluated by measuring serum KL-6, which is a clinically useful indicator for IP. The Th1/ Th2 balance and the CD4(+)/CD8(+) ratio were determined for lymphocytes obtained from BAL by flow cytometric analysis. In IPF patients, the CD4(+)/CD8(+) ratio was lower than in CVD patients. IPF patients showed Th2 dominance and CVD patients showed Th1 dominance when IP was active as evaluated by the serum KL-6 level. These data indicated that the Th1/Th2 balance of CD4(+) T cells in the BAL differs between active IPF and CVD, even though KL-6 is elevated in both diseases. Therefore, the Th1/Th2 profile should be investigated to determine the use of Th1/Th2 modulator therapy for active IP with elevation of KL-6.
TL;DR: Ex vivo-induced level of inflammatory cytokine IL-18 was significantly lower in the TCM group than in the placebo group after taking the capsules for 24 weeks, suggesting Lingzhi and San-Miao-San capsules might exert a beneficial immunomodulatory effect in patients with rheumatoid arthritis.
Abstract: Rheumatoid arthritis (RA) is an autoimmune joint disease. We evaluated a standard preparation of Lingzhi (Ganoderma lucidum) and San-Miao-San (Rhizoma atractylodis, Cortex phellodendri, Radix achyranthes bidentatae) capsules (TCM group) for its supplementary treatment efficacy for RA. There was no significant difference in the absolute count, percentage, and ratios of CD4(+)/CD8(+)/natural killer/B lymphocytes between the TCM and placebo groups after taking the capsules (all p > 0.05). There was no significant change in concentrations of plasma cytokines of interferon-gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1, monokine induced by IFN-gamma, regulated upon activation normal T-cell expressed and secreted, interleukin (IL)-8, and IL-18 after taking the capsules for 8 and 24 weeks (all p > 0.05). The percentage change in ex vivo-induced level of inflammatory cytokine IL-18 was significantly lower in the TCM group than in the placebo group after taking the capsules for 24 weeks (p < 0.05). Therefore, Lingzhi and San-Miao-San capsules might exert a beneficial immunomodulatory effect in patients with rheumatoid arthritis.
TL;DR: TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD, however, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.
Abstract: Tumor necrosis factor alpha (TNFalpha) in intestinal mucosa plays a key role in the inflammation characterizing Crohn's disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFalpha and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFalpha and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFalpha and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFalpha in CD. In conclusion, TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.
TL;DR: It is demonstrated that one of the potentially beneficial antitumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-γ secretion by T lymphocytes.
Abstract: The mushroom Phellinus linteus (PL) has been shown to have antitumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-gamma (IFN-gamma) by T lymphocytes. T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks and then stimulated with the mitogen concanavaline A (Con A). IFN-gamma gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-gamma was measured by enzyme-linked immunosorbent assay. WEPL significantly enhanced the transcription of IFN-gamma mRNA. The effect of WEPL on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracellular IFN-gamma protein as well as the secretion of IFN-gamma. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Our results demonstrate that one of the potentially beneficial antitumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-gamma secretion by T lymphocytes.
TL;DR: Results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.
Abstract: Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased ...
TL;DR: The expected B cell-specific pharmacological effects of TACI-Ig are demonstrated in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance and it is concluded that non-B cell related antiviral competence remains intact during TACi-IG treatment.
Abstract: TACI-Ig is a soluble glycoprotein comprised of a human IgG1-Fc fused with the extracellular domain of the human TACI receptor. Chronic exposure to TACI-Ig is associated with reduced circulating B cells in mouse and non-human primates, and a concomitant decrease in circulating immunoglobulin. Because of these activities, TACI-Ig is in clinical evaluation for treatment of various autoimmune diseases and B cell malignancies. In this study, the effect of TACI-Ig treatment on the ability of C57Bl/6 mice to clear influenza virus was evaluated. C57Bl/6 mice were exposed to vehicle (negative control), dexamethasone (positive control), or TACI-Ig (0.05, 0.50, or 5.0 mg/kg, SC, thrice weekly) from within one week prior to viral exposure through 21 days thereafter. Dexamethasone treatment of influenza-infected mice prolonged the infection, and decreased survival, body weight, lymphoid organ weight, influenza-specific IgM and IgG, and viral clearance relative to control animals, consistent with its expected immunosuppressive activity. Animals treated with TACI-Ig (0.05, 0.50, and 5.0 mg/kg) demonstrated a dose-dependent decrease in spleen weight and influenza-specific IgG and IgM in both lung and serum relative to control animals. In addition, flow cytometric analyses showed a decrease in B cells, but not T cells, in peripheral blood in animals treated with TACI-Ig. However, neither viral clearance nor survival was affected by TACI-Ig treatment. These data demonstrate the expected B cell-specific pharmacological effects of TACI-Ig in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance. It is concluded that non-B cell related antiviral competence remains intact during TACI-Ig treatment.
TL;DR: This study transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 ζ chain to demonstrate that NK92.HER-2/nei/ζ cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2-neu expressing cancers.
Abstract: NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have been previously reported to lyse HER-2/neu positive tumor cell lines through direct cell to cell contact. In the present study we have transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 ζ chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/ζ) specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both in vitro and in preclinical tumor models in vivo. More important we demonstrate that NK92.HER-2/neu/ζ cells constitutively secrete high levels of soluble scFv which mediate strong tumor cytostatic effects by directly binding on cell surface HER-2/neu. Our data uncover an additional mechanism through which NK92.HER-2/neu/ζ cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2/neu expressing cancers.
TL;DR: Thalidomide suppressed T NF-α, but when some RR patients' cells were stimulated with AFB, it enhanced TNF-α.
Abstract: Hypersensitivity reactions called reversal reaction (RR) and erythema nodosum leprosum (ENL) occur in leprosy. They are characterized by an increase in tumor necrosis factor-alpha (TNF-α). Thalidomide is an effective treatment for ENL but not RR. Its effectiveness in ENL is attributed to inhibition of TNF-α, and this does not explain its failure to treat RR. We assessed thalidomide's effect on TNF-α in RR. Mononuclear cells from RR and non-RR patients and healthy individuals were treated with thalidomide and M.leprae (AFB), a cytosol fraction of M. leprae or Dharmendra lepromin. Thalidomide suppressed TNF-α, but when some RR patients' cells were stimulated with AFB, it enhanced TNF-α.
TL;DR: The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects and suggest the antioxidative and antinflammatory properties of pioglitazone.
Abstract: There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (...
TL;DR: The first case, at the best of the knowledge, of a wide invasive malignant thymoma (type B3), associated with myasthenia gravis and hyperparathyroidism caused by parathyroid adenoma is reported.
Abstract: There are few cases described in the world literature reporting an association of thymoma (with myasthenia gravis or not) with hyperparathyroidism. In these cases the hyperparathyroidism was due to the presence of an adenoma or hyperplasic parathyroid tissue either in the cervical region or in an ectopic intrathymic location.(12345) In other cases the syndrome of hypercalcemia was due to the secretion of parathyroid-related protein (PTHRP) (6) or parathyroid hormone (PTH) (7) by the thymoma itself. We report the first case, at the best of our knowledge, of a wide invasive malignant thymoma (type B3), associated with myasthenia gravis and hyperparathyroidism caused by parathyroid adenoma.
TL;DR: In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1beta, IL-6,IL-10 and tumor necrosis factor alphaalpha from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H2O2.
Abstract: The commercially available HERBSnSENSEStrade mark Cordyceps (HSCS) belongs to a cultivated strain of Cordyceps sinensis whose immunomodulatory activities has been renowned in traditional Chinese medicine (TCM) for centuries. The present report is the first that describes its immunomodulatory features through a series of in vitro and in vivo experiments. We measured, in peripheral blood mononuclear cells the in vitro effects of HSCS on the gene expression of cytokines and cytokine receptors, cytokine release, and surface expression of cytokine receptors using cDNA expression array, cytometric bead array (CBA), and immunoflorescence staining, respectively, as well as macrophage phagocytosis and monocyte production of H2O2 using flow cytometry. Sixty female BALB/c mice were fed with either HSCS (40 mg/kg/day) or water consecutively for 14 days. Proliferation, cytokine liberation, and CD3/4/8 expression of splenic cells were measured using 5-bromo-2'-deoxyuridine proliferation ELISA, CBA, and cytometry immunoflorescence staining, respectively. In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1beta, IL-6, IL-10 and tumor necrosis factor alphaalpha from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H2O2. In vivo results showed that HSCS did not induce splenomegaly and cytokine overliberation. Our results possibly provide the biochemical basis for future clinical trials.
TL;DR: It is demonstrated that the bursa may play a role in androgen-active endocrine disrupting chemical-induced immunosuppression in birds by demonstrating that chicks treated with DDE were larger than, had fewer follicles, and exhibited vacuolization within follicles compared with controls.
Abstract: We hypothesized that immunosuppression in birds that is caused by exposure to antiandrogenic chemicals occurs mainly through disruption of the development of the androgen-sensitive avian lymphoid organ, the bursa of Fabricius. Injections of 20.0 or 40.0 μg of p,p′-DDE [ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)], an antiandrogen, were administered at embryonic day 1. Bursas from only chicks treated with DDE were larger than, had fewer follicles, and exhibited vacuolization within follicles compared with controls; spleens were unaffected. No differences in either immune response test were observed. This study demonstrates that the bursa may play a role in androgen-active endocrine disrupting chemical-induced immunosuppression.
TL;DR: Data suggest that a low-grade inflammation of the intestinal wall is always present in CD and UC patients, which may predict a clinical relapse risk, and reduced PMN and/or MØ trafficking from peripheral blood to intestinal mucosa with age by effects of chronic treatment should not be ignored in CD patients.
Abstract: Nowadays, calprotectin, a cytoplasmatic protein, released by activated neutrophilic polymorphonuclear cells (PMN) and/or monocytes-macrophages (MO), is considered a good indicator of inflammation in several diseases. Accordingly, fecal calprotectin represents a good predictor of clinical relapse in ulcerative colitis (UC) patients, whereas conflicting results have been reported in Crohn's disease (CD) patients. In our study, in 76 IBD patients (29 CD and 47 UC) fecal calprotectin has been evaluated by a commercial ELISA kit. Results demonstrate that levels of this protein in the stool are significantly more elevated in active CD and UC patients than in normal volunteers. In quiescent CD and UC a trend to higher levels of calprotectin than in the normal counterpart is, however, evident. These data suggest that a low-grade inflammation of the intestinal wall is always present in CD and UC patients, which may predict a clinical relapse risk. In the same group of patients calprotectin levels also were analyze...
TL;DR: Results showed a remarkable in vitro antibacterial property of bDLE against several pathogenic bacteria.
Abstract: The rapidly developing resistance of many infectious pathogenic organisms to modern drugs has spurred scientists to search for new sources of antibacterial compounds. One potential candidate, bDLE (dialysis at 10 to 12 kDa cut-off) and its fractions (“S” and “L” by 3.5 kDa cut-off and I, II, III, and IV by molecular exclusion chromatography), was evaluated for antibacterial activity against pathogenic bacterial strains (Staphylococcus aureus, Streptococcus pyogenes, Lysteria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi) using standard antimicrobial assays. A minimum inhibitory concentration (MIC) of bDLE and its fractions was determined by agar and broth dilutions methods. Only bDLE and its “S” fraction had an effect upon all bacteria evaluated (MIC ranging from 0.29 to 0.62 U/ml), and the bactericidal and bacteriostatic effects (evaluated by MTT assay) were bacterial species-dependent. These results showed a remarkable in vitro antibacterial property of bDLE against sever...
TL;DR: In vitro effects of two widely used UV-filters on the production of interferon (IFN)-γ and interleukin (IL)-10, two cytokines representing Th1- and Th2-type response, respectively, by activated murine splenocytes are studied.
Abstract: Chemical ultraviolet light absorbers (UV-filters) are nowadays widely used in cosmetic and plastic industry. Recent in vitro and in vivo studies have reported that certain chemical UV-filters possess estrogenic activity raising the question of whether these compounds are safe to human health. Work on estrogenic effects of these compounds, however, has focused mostly on reproductive organs, and as the presence of estrogen receptors has been identified in several cells of the immune system, UV screens also may have a great impact on immunity. Thus, we have studied the in vitro effects of two widely used UV-filters—benzophenone-2 (BP-2) and octyl-methoxycinnamate (OMC)—on the production of interferon (IFN)-γ and interleukin (IL)-10, two cytokines representing Th1- and Th2-type response, respectively, by activated murine splenocytes. Cells were cultured on 48-well plastic plates and stimulated with 12-miristate 13-acetate (PMA) (5 ng/ml) and ionomycin (50 ng/ml) in the presence of different concentrations (10...
TL;DR: STA-1 could effectively suppress the Der p 5-induced allergic reactions, and the availability of STA-1 for the treatment of allergic asthma was demonstrated in this study.
Abstract: The availability of STA-1 in suppressing allergen-induced immunoglobulin E (IgE) synthesis, airway inflammation and hyperreactivity in a murine model was investigated. The mice were intraperitoneally sensitized with Dermatophagoides pteronyssinus group 5 allergen (Der p 5) and orally treated with 300 mg/kg of STA-1 every other day for 14 days. The Der p 5-specific immunologic responses including changes of specific immunoglobulin G and E, cells in the broncholarvage fluid, and airway hyperreactivity were measured when mice received inhalation challenge with Der p 5 after sensitization for 21 days. By comparing with sham-treated groups, the synthesis of Der p 5-specific IgE was downregulated while the influx of eosinophils and neutrophils in the airway were remarkably reduced. In addition, Der p 5-induced airway hyperreactivity also was significantly eliminated by STA-1 treatment. These results showed that STA-1 could effectively suppress the Der p 5-induced allergic reactions, and the availability of STA-1 for the treatment of allergic asthma was demonstrated in this study.
TL;DR: The results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.
Abstract: In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.
TL;DR: A single dose of IMUNOR®, a low-molecular-weight immunodulator prepared from disintegrated and ultrafiltered pig leukocytes, was found to enhance recovery of murine pool of hemopoietic progenitor cells for granulocytes and macrophages damaged by a single injection of cytotoxic drugs 5-fluorouracil or cisplatin.
Abstract: A single dose of IMUNOR, a low-molecular-weight immunodulator prepared from disintegrated and ultrafiltered pig leukocytes, was found to enhance recovery of murine pool of hemopoietic progenitor cells for granulocytes and macrophages damaged by a single injection of cytotoxic drugs 5-fluorouracil or cisplatin. The best results were obtained after the treatment with IMUNOR on days 3 or 4 after the injection of 5-fluorouracil or cisplatin. These results together with previous findings obtained in our laboratory suggest that IMUNOR has the potential to become a part of treatment schemes in oncological practice aimed at alleviation of myelosuppression evoked by cytotoxic anti-tumor therapy.