Showing papers in "Immunopharmacology and Immunotoxicology in 2001"
TL;DR: The mechanisms responsible for gram-positive and gram-negative sepsis in the splenectomized host and possible therapeutical approaches able to neutralize bacterial products endowed with noxious effects are discussed.
Abstract: Over the past few years, many observations of overwhelming post splenectomy bacterial infections have been reported. Streptococcus pneumoniae is the aetiologic agent in about 80% of cases, but also gram-negative bacteria are involved in the development of fatal infections in splenectomized patients. Functionally, the spleen plays a fundamental role in bacterial clearance either by antibody response or macrophage bactericidal capacity. At the same time, there is evidence that the spleen also contributes to bacterial endotoxin detoxification. Finally, the mechanisms responsible for gram-positive and gram-negative sepsis in the splenectomized host and possible therapeutical approaches able to neutralize bacterial products endowed with noxious effects are discussed.
115 citations
TL;DR: Evaluated circulating proinflammatory cytokines and gastrin levels in H. pylori positive asymptomatic subjects showed significantly higher gastrin and TNF-α levels than uninfected subjects, while IFN-γ and IL-10 circulating levels were not affected by H.pylori presence, being not significantly different in the two groups.
Abstract: The pathophysiology of hypergastrinemia in H. pylori infection has been largely investigated and different reports clearly show that the infected antrum has a marked inflammatory response with a suggestive local production of cytokines. Notwithstanding, a few data are available on the circulating levels of cytokines and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)-8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)-alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H. pylori negative ones. To this end, thirty healthy volunteers with no digestive symptoms or systemic disease were enrolled and H. pylori infection was identified by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured with a solid-phase ELISA. Fifteen infected people showed significantly higher gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8 levels were significantly higher in the uninfected subjects than in H. pylori positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not affected by H. pylori presence, being not significantly different in the two groups.
71 citations
TL;DR: Data clearly show that Spirulina platensis feeding upregulates macrophage phagocytic as well as metabolic pathways leading to increased nitric oxide synthase activity, implying that Spirula platensis may enhance the functions of mononuclear phagcytic system thereby increasing the disease resistance potential in chickens.
Abstract: The effects of dietary Spirulina platensis on chicken macrophage phagocytic function and nitrite production were examined. Day old broiler (meat-type) chicks were randomly assigned to various pens of electrically heated wire batteries. Dietary treatment groups included a basal diet with no dietary Spirulina added, and three additional groups with 0.5, 1.0 and 2.0% dietary Spirulina. Feed and water were provided for ad libitum consumption from one day of age. Sephadex®-elicited macrophages were harvested at 14, 35 and 42 days of age. Phagocytosis assay was performed by co-incubating sheep red blood cells (SRBC) with the adherent macrophage monolayers. For nitrite quantification, macrophage cultures from various dietary treatment groups were stimulated in the presence or absence of 1 μg/mL of Escherichia coli lipopolysaccharide. These culture supernatant fractions were then tested for nitrite levels using the Greiss reagent technique. All Spirulina dietary group macrophages exhibited an enhanced phagocytic ...
69 citations
TL;DR: Results suggest a protective antitumor effect of CVE which might be attributable, at least in part, to the stimulation of the production and, possibly, maturation of granulocytes and macrophages.
Abstract: Chlorella vulgaris extract (CVE) was examined for its effects on the Ehrlich ascites tumor-induced suppression in the numbers of bone marrow and spleen granulocyte-macrophage progenitor cells (CFU-GM) in mice. No effects on bone marrow and spleen CFU-GM, as compared to controls, were observed in normal mice given 50, 100 and 200 mg/kg CVE orally for 5 days. In tumor-bearing mice, myelosuppression concomitant with increased number of spleen CFU-GM were observed. The number of CFU-GM in the bone marrow was restored to control levels after the administration of CVE (50, 100 and 200 mg/kg) to tumor-bearing mice, and a slight reduction in spleen colony formation was observed in these animals. In addition, CVE significantly prolonged the survival of mice inoculated with the Ehrlich ascites tumor. These results suggest a protective antitumor effect of CVE which might be attributable, at least in part, to the stimulation of the production and, possibly, maturation of granulocytes and macrophages.
68 citations
TL;DR: The results of the present experiment suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation, and are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells bydiazepam, thereby increasing the serum levels of cortic testosterone and thus reducing CIPE.
Abstract: Carrageenin causes a reproducible inflammatory reaction and remains the standard irritant for examining acute inflammation and anti-inflammatory drugs. High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin administration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosterone on the anti-inflammatory effects of diazepam. Five experiments were conducted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on carrageenin-induced paw edema (CIPE), pleurisy and increase in vascular permeability in rats. Results showed that: 1. diazepam or Ro5-4864 (a PBR agonist) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-benzodiazepine PBR antagonist) suppressed the effects of either diazepam or Ro5-4864 on CIPE; 3. diazepam reduced the volume of the pleural exudate in carrageenin-injected rats, as well as its leukocyte count; 4. diazepam treatment reduced the magnitude of the increase in vascular permeability caused by carrageenin; 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticosterone. These results suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.
54 citations
TL;DR: Results show that treatment of mast cells with estrogen prevented PMA or A23187-stimulated TNF-α or IL-6 release, providing evidence for a potent inhibition of cytokines by estrogen in human mast cells.
Abstract: Estrogens are important for bone homeostasis and are classified as anti-resorptive agents. In ovariectomized rats, mast cell changes occurred during the activation of resorption. In addition, quantitative changes occurred in mast cell population residing near the site undergoing resorption. Considering these studies, mast cells may play a role in osteoporosis. Therefore, it is of paramount importance to study mast cell cytokine production also in the presence or absence of estrogen. When cultured in the absence of estrogen, human mast cells treated with PMA or A23187 demonstrated significantly greater release of TNF-alpha and IL-6 than cells grown under estrogen-depleted condition. Our results show that treatment of mast cells with estrogen prevented PMA or A23187-stimulated TNF-alpha or IL-6 release. These data provide evidence for a potent inhibition of cytokines by estrogen in human mast cells. This study may help to explain the association between mast cells and osteoporosis.
53 citations
TL;DR: The findings indicate that neuropeptides have modulating effects on macrophage-L.
Abstract: Host-parasite interactions and their outcome constitute a critical and challenging step in disease establishment in cutaneous leishmaniasis. In the present in vitro study we investigated the possible modulating effects of both sensory and autonomic neuropeptides that normally exist in human and mouse skin, on the uptake and leishmanicidal capacity of macrophages on Leishmania (L.) major parasites, using a monocyte/macrophage murine cell line (Raw 264.7). The sensory neuropeptides somatostatin (SOM), calcitonin gene-related peptide (CGRP) and substance P (SP) suppressed the macrophage capacity for phagocytosing L. major promastigotes at different concentrations, 10(-10) - 10(-5) M, however, the suppressive effect of SP does not reach a significant level. CGRP and SP enhanced the leishmanicidal capacity of macrophages at 10(-7) M, and 10(-5) M, respectively, whereas SOM was without effect. The autonomic neuropeptides vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) both suppressed the phagocytic and leishmanicidal capacities of macrophages at various concentrations, 10(-10) - 10(-5) M. The findings indicate that neuropeptides have modulating effects on macrophage-L. major interactions. These effects might be exerted by a direct action on macrophages or indirectly through induction of other mediators.
46 citations
TL;DR: The results suggest that during the initial hours of exposure to podophyllotoxin or specific analogs these compounds do not act as independent stimulants of human monocyte activation, but can selectively enhance or suppress LPS-induced cytokine gene expression.
Abstract: There exists a growing body of research which indicates that antimitotics such as taxol and colchicine influence cytokine gene expression. In the present study we examined the effect of podophyllotoxin and six analogs on nuclear factor kappa B (NF-kappa B) activation, and on interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression in human THP-1 monocytes. All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin. The remaining three analogs (podophyllotoxin-4-O-glucoside, beta-peltatin-beta-D-glucopyransoide and 1,2,3,4-dehydrodesoxypodophyllotoxin) were inactive. Clearly certain structural features such as the presence of a glycosidic group or ring aromatization results in loss of biological activity. Interestingly, the analogs that were inactive in our assays have also been previously shown to lack affinity for tubulin binding. These results suggest that during the initial hours of exposure to podophyllotoxin or specific analogs these compounds do not act as independent stimulants of human monocyte activation, but can selectively enhance or suppress LPS-induced cytokine gene expression.
44 citations
TL;DR: Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.
Abstract: Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3−HLADR+, CD3−CD69+ and CD14+CD16−, and significantly lower percentages of CD3− and CD8−CD28+ cells. After one cycle of AT, the absolute numbers of CD3+, CD3−CD4−, CD3+CD8+ and CD8−CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.
42 citations
TL;DR: It is observed that pre-treatment with SB203580, a selective p38 MAP kinase (p38 MAPK) inhibitor, attenuated the hypoxia-induced apoptosis.
Abstract: The aim of this study is to elucidate the possible mechanism of apoptosis in response to hypoxia in MC3T3E1 osteoblasts. MC3T3E1 osteoblasts under hypoxic conditions (2% oxygen) resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent dye, Hoechst 33258. Pretreatment with Z-VAD-FMK, a pan-caspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to hypoxia. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm what caspases are involved in apoptosis, western blot analysis was performed using anticaspase-3 or -6 antibody. The 10-kDa protein, corresponding to the active products of caspase-3 and the 10-kDA protein of the active protein of caspase-6 were generated in hypoxia-challenged cells in which processing of the full length form of caspase-3 and -6 was evident. With a time cou...
37 citations
TL;DR: The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible, Thus, C'sA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.
Abstract: Chronic Idiopathic Urticaria (CIU) is a cutaneous disorder for which there is no identifiable specific etiologic agent. Some recent evidences suggest that CIU might be an autoimmune disease. We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A (CsA) treatment in patients unresponsive to antihistaminic treatment. Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups. CsA was prescribed for group 1 and Prednisone for group 2 as control, for 8 weeks. Before and after the therapy we performed on all patients immunological studies. For all patients symptoms disappeared after a few days of therapy. Before therapy all patients showed activated B cells (CD19+CD23+ cells) and among B CD19+ cells, about 20% were CD5+ (cells that synthesize natural autoantibodies). After treatment with Prednisone in group 2, a significant reduction of CD4+ lymphocytes (p = 0,01) was observed. Our findings might support the CIU autoimmune pathogenetic hypothesis. The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible. Thus, CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.
TL;DR: Results indicate that PVAE inhibits immediate-type allergic reactions in rats, and has a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-α production from RPMC.
Abstract: We studied the effect of aqueous extract of Prunella vulgaris (Labiatae) (PVAE) on immediate-type allergic reactions. PVAE (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylactic shock i...
TL;DR: It is concluded that the study provided no supporting evidence for immunostimulatory activity by the echinacea preparations and, in fact, may be immunosuppressive under some conditions.
Abstract: This study evaluated acquired-immune functions representing the three major branches of the immune system in male rats fed a commercially available echinacea product. An additional comparison of effects on antibody formation in male and female rats was done using the commercial echinacea product and two echinacea tinctures marketed by local herbalists. In initial testing, we found no evidence of altered natural killer cell activity, T cell-mediated delayed-type hypersensitivity, or specific antibody formation in male rats given either a 225 mg/kg or 50 mg/kg of the commercial echinacea for 6 weeks. Antibody formation was significantly suppressed in female but not male rats given 250 mg/kg for 2 weeks of the commercial echinacea. The local products tested had no effect on antibody formation. We concluded that our study provided no supporting evidence for immunostimulatory activity by the echinacea preparations we examined and, in fact, may be immunosuppressive under some conditions.
TL;DR: The studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases and dose-dependently inhibited compound 48/80-induced systemic allergy.
Abstract: The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.
TL;DR: The overall results suggest that β-endorphins may down modulate T-cell antibacterial response in HCV and in IBD patients by saturating peripheral receptors on immune cells.
Abstract: Naloxone acts as an opioid antagonist, displacing opioid drugs from cellular receptors. Among opioid substances, β-endorphins are able to bind to several cell receptors, even including those expressed by immune cells. In this respect, evidence has been provided that in the course of viral infections, as well as in patients with ulcerative colitis high levels ofβ-endorphins are detectable. Here, peripheral blood lymphocytes (PBL) from 21 HCV infected patients and 14 patients with IBD, respectively, were incubated with Naloxone and Naloxone + Ca2+ in order to evaluate a putative modulation of PBL-mediated antibacterial activity. In fact, previous studies have demonstrated a reduction of this T-cell activity in HCV and IBD patients.In general terms, the above treatment led to a recovery of the depressed antibacterial activity. In some cases, increase in T lymphocyte function was obtained with Naloxone alone, while in other cases the combination Naloxone + Ca2+ gave rise to a restorative effect. Of note, in s...
TL;DR: It is suggested that the anti-asthmatic effects of MXGST are mainly due to its stimulation of β2-adrenoceptors on bronchial smooth muscle and its anti-inflammatory ability to inhibit the neutrophil into the airway.
Abstract: Ma-Xing-Gan-Shi-Tang (MXGST), a traditional Chinese medicine, has been used in treatment of the bronchial asthma for several centuries. However, the therapeutic mechanisms of this Chinese medicine are still far from clear. To understand the mechanism of anti-asthmatic property of MXGST, a guinea pig model of allergic asthma was used to investigate the effects of MXGST on Dermatophagoides pteronyssinus-induced early and late asthmatic responses and airway inflammation, and examine direct beta2-adrenoceptor agonist activity in guinea-pig isolated trachea. Administration of MXGST (10 g/kg) extracts significantly inhibited the antigen induced immediate asthmatic responses (IAR) in actively sensitized guinea pig. MXGST caused concentration-dependent relaxation in strips of guinea pig trachea contracted with carbachol, and ICI-118551, a selective beta2-adrenoceptor antagonist, significantly inhibit the relaxation caused by MXGST. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that MXGST significantly inhibited the increase in neutrophil in the airway at 1, 6 and 24 hr after antigen challenge. Histopathologic examination results showed that MXGST suppressed the neutrophil infiltration into lung tissue. In conclusion, we suggest that the anti-asthmatic effects of MXGST are mainly due to its stimulation of beta2-adrenoceptors on bronchial smooth muscle and its anti-inflammatory ability to inhibit the neutrophil into the airway. The precise mechanism of action of MXGST in asthma remains to be elucidated.
TL;DR: The results confirm the good tolerability of nimesulide and paracetamol in patients who experienced urticaria/angioedema caused by NSAIDs, however, the risk of reaction to these alternative study drugs is statistically increased by a history of chronic Urticaria and, above all, by aHistory of NSAID-induced angioedEMA.
Abstract: Previous studies evaluated the tolerance of nimesulide and paracetamol in subjects with cutaneous, respiratory and anaphylactoid reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). In this study we investigated tolerability and reliability of nimesulide and paracetamol in a very large number of patients with an exclusive well-documented history of NSAID-induced urticaria/angioedema. Furthermore, we evaluated whether some factors have the potential to increase the risk of reaction to paracetamol and nimesulide. A single-placebo-controlled oral challenge procedure with nimesulide or paracetamol was applied to 829 patients with a history of NSAID-induced urticaria/angioedema. A total of 75/829 (9.4%) patients experienced reactions to nimesulide or paracetamol. Of the 715 patients tested with nimesulide 62 (8.6%) showed a positive test, while of 114 subjects submitted to the challenge with paracetamol, 13 (9.6%) did not tolerate this drug. Furthermore, 18.28% of patients with a history of chronic urticaria and 11.8% of subjects with an history of NSAID-induced urticaria/angioedema or angioedema alone (with or without chronic urticaria) resulted to be intolerant to alternative drugs. Taken together, our results confirm the good tolerability of nimesulide and paracetamol in patients who experienced urticaria/angioedema caused by NSAIDs. However, the risk of reaction to these alternative study drugs is statistically increased by a history of chronic urticaria and, above all, by a history of NSAID-induced angioedema.
TL;DR: It is suggested that Siegesbeckia orientalis have antiallergic activity by inhibition of IgE production from B cells by using U266B1 human IgE-bearing B cells.
Abstract: Elevated levels of immunoglobulin (Ig) E are associated with immediate-type allergic reactions. Jin-deuk-chal is the whole plant of Siegesbeckia orientalis (SO) sL. Immunization of mice with small amounts of protein antigens on alum results in several fold increases in total plasma IgE, much of it specific for the immunizing antigen. In the present study, we investigated the effect of Siegesbeckia orientalis (SO) on IgE production. SO inhibited the plasma levels of IgE induced by antigens. The effects of SO on the interleukin (IL)-4-dependent IgE response by mouse whole spleen cells were studied. IL-4 dependent IgE production of lipopolysaccharide (LPS)-stimulated whole spleen cells was inhibited by SO. In addition, using U266B1 human IgE-bearing B cells, we found that SO inhibited the production of IgE activated by LPS plus IL-4. These results suggest that SO have antiallergic activity by inhibition of IgE production from B cells.
TL;DR: An inhibition of JNK1 in the system is involved in the protection of H2O2-induced apoptosis in H9C2 cardiomyoblasts.
Abstract: Nitric oxide (NO) attenuates hydrogen peroxide (H2O2)-mediated injury to H9C2 cardiomyoblasts. To examine the role of nitric oxide, cultured H9C2 cardiomyoblasts were treated with H2O2 for 2 h in the presence or absence of the NO donor, diethylamine nitric oxide (DEANO). DEANO (30 microM) attenuated H2O2-induced apoptosis in H9C2 cells. H2O2-exposed H9C2 cells resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay, nuclear morphology stained with fluorescent dye, Hoechst 33258 and Annexin V staining. Pretreatment with z-VAD-FMK, a pancaspase inhibitor, or z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to H2O2. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. Treatment of H9C2 cells with 100 microM H2O2, resulted in a strong activation of JNK/SAPK. However, the activation of JNK/ SAPK was clearly attenuated by 30 microM DEANO. Furthermore, the dominant negative JNK and SEK1-expressing cells displayed a marked decrease in a number of apoptotic cells. This inhibition of JNK1 in the system is involved in the protection of H2O2-induced apoptosis in H9C2 cardiomyoblasts.
TL;DR: Results demonstrate that C. ferrea extract acts as a positive regulator of myelopoiesis, and suggest that the therapeutic effect of C. Ferrea may be partially mediated by this action, and demonstrate that infected and tumor-bearing mice treated with 500 and 1000 mg/kg of Caesalpinia ferrea aqueous extract significantly stimulated myelobiology.
Abstract: The capacity of hematopoietic tissues to produce and mobilize phagocytes to the site of infection and tumor growth is of central importance to mediate the early immunological response. In this pers...
TL;DR: The results obtained suggest that both immunosuppressive drugs exhibit dose-dependent inhibitory effect on NO production and that FK 506 is more potent agent than CsA, in this respect.
Abstract: The modulatory effect of FK 506 and cyclosporin A (CsA) on the expression of inducible nitric oxide synthase (iNOS) in macrophages and mechanisms of their action were analysed. Isolated rat peritoneal macrophages were cultured for 12 or 24 h with or without lipopolysaccharide (LPS) (5 μg/ml) and in the absence or presence of FK 506 or CsA (0.1 and 1 μg/ml). Total RNA from macrophages was isolated and the expression of the gene for iNOS was assessed by using RT-PCR. The concentration of NO2− in culture supernatants was taken as a measure of nitric oxide (NO) production. FK 506 (0.1 and 1 μg/ml) reduced the LPS-induced increase of NO2− levels by 68% and 81%, respectively. CsA (0.1 and 1 μg/ml) decreased levels of nitrites by 39% and 69%, respectively. The results obtained suggest that both immunosuppressive drugs exhibit dose-dependent inhibitory effect on NO production and that FK 506 is more potent agent than CsA, in this respect. FK 506 exhibits its inhibitory effect on a phosphatase at the transcription...
TL;DR: The results suggest that the IFN-γ-differentiation of U937 cells increases the susceptibility to mistletoe lectin-II-induced apoptosis.
Abstract: Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album coloratum), is known as a potent apoptosis inducer. The previous research has demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Jun N terminal kinase (JNK) activation in human myeloid U937 cells. The purpose of this research is to prove the synergistic action of mistletoe lectin-II and interferon-γ (IFN-γ) in the apoptotic cytotoxicity of U937. When U937 cells were treated with mistletoe lectin-II after being differentiated by IFN-γ, the proteolytic activity of caspase-3 and 9 was markedly elevated and that of caspase-8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however, not activated during the resting phase and nor in IFN-γ-differentiated U937 cells. Western blot analysis revealed that, in IFN-γ-differentiated U937 cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the apoptotic sensiti...
TL;DR: It is indicated that Tα1 is stimulatory for both humoral and cellular immune responses, thus providing the immunological basis for the clinical benefit of this compound.
Abstract: Thymosin alpha1 (Talpha1) is an oligopeptide hormone originally isolated from the thymus gland, and has been reported to have stimulating effects on the differentiation of T cells and NK cells. These immunostimulating properties have been considered to be useful for improving immune disorders associated with various diseases including cancer, AIDS and hepatitis. Here, we characterized immunostimulating properties of Talpha1 in experimental immunodeficiency of mice that was induced by the administration of cyclophosphamide (CY). Repeated injection of 30-300 microg/kg/day of Talpha1 after CY-treatment significantly accelerated the restoration of the reduced number of CD4+CD8+ T cells in the thymus. Talpha1 administration was effective in restoring the suppressed activities of helper T cells and cytotoxic T cells in CY-treated mice. Talpha1 also had stimulating effects on reduced activity of lymphokine-activated killer cells in CY-treated mice. These results indicate that Talpha1 is stimulatory for both humoral and cellular immune responses, thus providing the immunological basis for the clinical benefit of this compound.
TL;DR: It seems that tolerance test may represent a valid approach to detect a safe antibiotic in patients with a history of immediate adverse reactions to antibiotics, and risk factors for MDAS are female sex and intolerance to NSAIDs.
Abstract: Multiple Drug Allergy Syndrome (MDAS) is a frequent clinical condition characterized by reactions to more than one different class of antibiotics. Even if some studies have previously reported an increased rate of allergic reactions to drugs in patients with a history of antimicrobials and NSAIDs allergy, risk factors and pathogenesis of MDAS are still object of investigation. Moreover, in these subjects it is often difficult to prescribe a safe alternative antibiotic without a tolerance test. In this study we carried out 504 tests in 460 patients with a history of immediate adverse reactions to antibiotics. From the analysis of our results it emerges that risk factors for MDAS are female sex and intolerance to NSAIDs. Risk factors for positive tolerance test are male sex, intolerance to NSAIDs and a history of MDAS, respectively. In conclusion, it seems that tolerance test may represent a valid approach to detect a safe antibiotic in these patients.
TL;DR: The role of neutrophil respiratory burst in the age-associated decline of cytotoxicity towards invading microorganisms and the role of oxidative metabolism in the increased incidence of apoptotic phenomena observed in neutrophils of aged following cell stimulation is discussed.
Abstract: During the last few years, several studies have pointed out the imbalance of immune responses with advancing age, this accounting for the increased susceptibility of elderly individuals to life-threatening diseases. This review is focussed on the role of neutrophil respiratory burst in the age-associated decline of cytotoxicity towards invading microorganisms. Particular emphysys is given to extracellular matrix proteins, acting as physiologic regulators of oxidative activity, as well as to neutrophil cytoskeleton, whose dysfunction is likely to be involved in the agonist-related defect of the coupling between β2-dependent adhesive and oxidative events occurring in the aging. The role of oxidative metabolism in the increased incidence of apoptotic phenomena observed in neutrophils of aged following cell stimulation is also discussed.
TL;DR: An immunoregulatory role for P. quitoc is suggested in counteracting the tumor-induced myelopoietic suppression as well as usefulness as adjuvant treatment of cancer.
Abstract: Progressive tumor growth is regularly accompanied by changes in the cellular constituents of the immune system. Evidence suggests that soluble factors generated during tumor growth can affect the amount of granulocytemacrophage progenitors. In vitro colony growth of progenitor cells may be an early indicator of the cellular changes associated with tumor growth. Pluchea quitoc has been previously found to modulate the hematopoietic response during bacterial infection. This study was designed to investigate the effects of P. quitoc on the growth and differentiation of bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in Ehrlich ascites tumor-bearing mice. In contrast to the myelosuppression developed in the tumor-bearing animals, treatment with P. quitoc ethanolic extract (250, 500 or 1000 mg/kg) for 3 consecutive days after tumor challenge reversibly stimulated myelopoiesis, restoring the number of CFU-GM to normal. This same dose-schedule also increased colony formation in normal mice as compar...
TL;DR: Findings suggest that the modulation of iNOS gene expression is another possible pathway by which retinoids may function as anti-inflammatory agents.
Abstract: Inflammation has been known to be associated with excess synthesis of nitric oxide (NO) by inducible NO synthase (iNOS). Retinoids have been reported to have anti-inflammatory activity, but the mechanism by which they can elicit this activity is poorly understood. The effects of retinoids on NO synthesis and iNOS gene expression in murine fibroblast L929 cells were examined. Treatment of the cells with interferon-y resulted in excess NO synthesis and iNOS gene expression. All-trans-retinoic acid significantly inhibited NO synthesis and iNOS gene expression in a dose-dependent manner. Similarly, 9-cis-retinoic acid also inhibited NO synthesis, but retinol did not show any inhibitory effect on NO synthesis. These findings suggest that the modulation of iNOS gene expression is another possible pathway by which retinoids may function as anti-inflammatory agents.
TL;DR: The frequency of drug-induced UA has tended to increase, being more prevalent in females and the majority of cases occuring during the third decade of life, and the most frequently involved drugs are anti-inflammatory and antimicrobial agents.
Abstract: Urticaria and angioedema (UA) represent a syndrome that is frequently encountered in children and adults. However, although they are often associated (in up to 50% of some patient populations), these two clinical entities should not be considered synonymous because they have distinct clinical and histopathological characteristics. The frequency of UA in drug-induced pathologies is quite high Here we report a retrospective survey of 2287 patients, observed between 1988 and 1997 presenting one or more episodes of drug-induced UA. In 1,973 patients (86.2%) [639 (32.4%) males and 1,334 (67.6%) females] a specific drug responsible for UA was identified. Particularly over the last two years the frequency of drug-induced UA has tended to increase, being more prevalent in females and the majority of cases (576: 23.1%) occuring during the third decade of life. The most frequently involved drugs are anti-inflammatory (particularly acetylsalicylic acid) and antimicrobial agents (mainly beta-lactams).
TL;DR: It was found that in a healthy elderly group, only 52% of whom responded to the influenza vaccine, endogenous levels of interleukin 6, IL-10 and gamma interferon did not differ statistically significantly between responders and non-responders.
Abstract: Cytokines play critical roles in regulating the antibody response to vaccines. We sought to understand the role of endogenous cytokines in the determination of antibody production in the elderly, a group of subjects known to have a lower response rate to vaccination. We found that in a healthy elderly group, only 52% of whom responded to the influenza vaccine, endogenous levels of interleukin 6 (IL-6), IL-10 and gamma interferon (IFNγ) did not differ statistically significantly between responders and non-responders (responders: n = 27, IL-6 = 293 ± 101 pg/ml, IL-10 = 882 ± 240 pg/ml; non-responders: n = 26, IL-6 = 223 ± 71 pg/ml, P = 0.57, IL-10 = 445 ± 148 pg/ml, mean ± SE, P = 0.14, respectively, and undetectable IFNγ). Serum levels of these three cytokines were not changed significantly four weeks after vaccination (P < 0.05 for IL-6 and P < 0.01 for IL-10). In addition, there were also no age-dependent differences in serum IL-6 and IL-10 levels.
TL;DR: It is suggested that the mechanism of cytoprotection of CsA on the cytosolic Ca2+ changes and ALT leakage induced by t-BHP, does not directly correlate with protection of t- BHP-induced changes of mitochondrial membrane potential.
Abstract: In the present work, we followed an in vitro protective action of cyclosporin A (CsA) against tert-butyl hydroperoxide (t-BHP)–induced oxidative damage in hepatocytes. Various parameters (cell viability, cytosolic calcium level, rhodamine 123 accumulation as indicator of mitochondrial membrane potential and alanine-aminotransferase leakage from cells) were measured as an index of cytotoxicity. Tert-butyl hydroperoxide (1 mM) significantly increased cytosolic Ca2+ and affected mitochondrial membrane potential. Pretreatment with cyclosporin A (0.5 μM) reduced t-BHP-induced cytosolic Ca2+ increase and ALT (alanine-aminotransferase) leakage, but had no protective effect on t-BHP-induced changes of mitochondrial membrane potential. Our data thus suggest that the mechanism of cytoprotection of CsA on the cytosolic Ca2+ changes and ALT leakage induced by t-BHP, does not directly correlate with protection of t-BHP-induced changes of mitochondrial membrane potential.