Showing papers in "Immunopharmacology and Immunotoxicology in 2010"
TL;DR: The potential for finding new treatments from marine natural products for inflammation, cancer, infections, and neurological disorders is described, and examples of such compounds and activities are outlined.
Abstract: Natural products, secondary metabolites, isolated from plants, animals and microbes are important sources for bioactive molecules that in many cases have been developed into treatments for diseases. This review will focus on describing the potential for finding new treatments from marine natural products for inflammation, cancer, infections, and neurological disorders. Historically terrestrial natural products have been studied to a greater extent and such classic drugs as aspirin, vincristine and many of the antibiotics are derived from terrestrial natural products. The need for new therapeutics in the four areas mentioned is dire. Within the last 30 years marine natural products, with their unique structures and high level of halogenation, have shown many promising activities against the inflammatory response, cancer, infections and neurological disorders. The review will outline examples of such compounds and activities.
137 citations
TL;DR: Oral administration of Nigella sativa oil before irradiation considerably normalized all the above-mentioned criteria; and produced significant regeneration in spleen and thymus lymphoid follicles.
Abstract: Background and aim: Sixty male Wistar rats, divided into 4 groups, 15 each, were designed as I-control rats, II-rats orally intubated with Nigella sativa oil (1 ml/kg b.wt./day) for 5 days/week, III-whole body gamma irradiated rats with the estimated LD50/30 (4 Gray) and IV-rats daily intubated with Nigella sativa oil then subjected to whole body gamma irradiation, to investigate the radioprotective potential of Nigella crude oil against hemopoietic adverse effects of gamma irradiation.Results: Irradiation resulted in significant reduction in hemolysin antibodies titers and delayed type hypersensitivity reaction of irradiated rats, in addition to significant leukopenia and significant decrease in plasma total protein and globulin concentrations and depletion of lymphoid follicles of spleen and thymus gland. Furthermore, there was a significant increase in malondialdehyde concentration with a significant decrease in plasma glutathione peroxidase, catalase and erythrocyte superoxide dismutase activities wer...
76 citations
TL;DR: An iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings has suggested how to modulate acute inflammation in a rational, individually optimized fashion.
Abstract: Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
72 citations
TL;DR: It is demonstrated that apigenin exhibits an anti-inflammatory activity in a murine asthma model, and can switch the immune response to allergens toward the Th1 profile.
Abstract: Many flavonoids were demonstrated to possess the antiallergic effect. Here we detected whether apigenin, a flavonoid, can attenuate allergen-induced airway inflammation and what is the possible mechanism in a murine model of asthma. Apigenin decreased the degree of the inflammatory cell infiltration, airway hyperresponsiveness, and total immunoglobulin E levels compared with the ovalbumin group. In addition, apigenin triggered the switching of the immune response to allergens toward a T-helper type 1 (Th1) profile. Our data clearly demonstrated that apigenin exhibits an anti-inflammatory activity in a murine asthma model, and can switch the immune response to allergens toward the Th1 profile.
68 citations
TL;DR: Curcumin, which was found in some plants, eliminated the effect of TCDD on immune system and body weight when it was given together with 2,3,7,8-TCDD, and it is thought that this effect may have occurred via curcumin and T CDD binding aryl hydrocarbon receptor (AhR) competitively.
Abstract: Background and aim: In this study, the negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the immune system and body weight gain of rats and the preventive effects of curcumin were examined.Material and methods: For this purpose, 128 3-4-month-old Wistar albino rats with 280-310 g body weights were used. The 2 μg/kg dose of 2,3,7,8-TCDD and 100 mg/kg dose of curcumin were dissolved in corn oil and orally given to the rats found in the experimental and control groups. Then, the serum samples were taken from all rats at 15, 30, 45 and 60 days to analyzed for the determination of TNF-α, IFN-γ, IL-12 and IL-13 levels by ELISA method. The data of body weight gain was measured at 15, 30, 45 and 60 days.Results: The results indicated that 2,3,7,8-TCDD caused a significant increase (p<0.05) in serum TNF-α level. However, it caused significant (p<0.05) decreases in the levels of IFN-γ, IL-12 and IL-13 in rats. On the contrary, curcumin increased IFN-γ, IL-12 and IL-13 levels, but decreased TNF-α lev...
63 citations
TL;DR: The impact of carbohydrate synthesis on the design of efficient carbohydrate-based antimicrobial and anticancer vaccines is illustrated and how immunological research can benefit from these novel tools provided by glycochemistry is focused on.
Abstract: Carbohydrates and glycoconjugates are involved in a number of biological processes including host-pathogen interactions, cell communication, proliferation and differentiation as well as the initiation of immune responses. However, access to synthetic oligosaccharide structures has been limited for long time since no standardized protocols for the synthesis of complex oligosaccharides from monomeric building block existed. Recent advances in glycochemistry and glycobiology have helped elucidate biological functions of carbohydrates. Novel methods such as automated synthesis of vaccine candidates and immunologically relevant carbohydrates have contributed to this success as well as high-throughput methods such as glycan arrays. This review illustrates the impact of carbohydrate synthesis on the design of efficient carbohydrate-based antimicrobial and anticancer vaccines. Furthermore, this review focuses on how immunological research can benefit from these novel tools provided by glycochemistry.
59 citations
TL;DR: Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation and blocked the induction of ER stress proteins, suggesting that metformin may protect hepatocytes from death induced by saturated fatty acids.
Abstract: The excessive supply of fatty acids to the liver contributes to hepatic insulin resistance and endoplasmic reticulum (ER) stress associated with obesity or type 2 diabetes mellitus. Furthermore, excess and/or prolonged ER stress contributes to hepatic cell death deteriorating nonalcoholic fatty liver disease to steatohepatitis. The aim of this study was to investigate the effects of metformin on palmitate-induced ER stress and hepatic insulin resistance in HepG2 cells. Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation. Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1. Metformin may therefore protect hepatocytes from death induced by saturated fatty acids. These data may also provide a further rationale for exploring the use of metformin in the treatment of non-alcoholic fatty liver disease, revealing its blocking effect for hepatic insulin resistance evoked by saturated fatty acids.
59 citations
TL;DR: The efficacy of fenugreek oil is revealed in the amelioration of diabetes, hematological status, and renal toxicity which may be attributed to its immunomodulatory activity and insulin stimulation action along with its antioxidant potential.
Abstract: Immunological disorders and nephropathy are among the most frequent and serious complications of diabetes mellitus. This shows that fewer infiltrated inflammatory cells evidenced by reverted back to near the normal value of white blood cell, mean corpuscular volume, and lymphocytes counts as interleukin-6 in pancreas. Also, fenugreek oil significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. The pancreatic islet and less β-cells damage were observed after the administration of fenugreek oil to diabetic rats. Moreover, diabetic rats showed low activities of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione content in kidney, which were restored to near normal levels by treatment with fenugreek oil. The increased levels of lipid peroxidation, creatinine, albumin, and urea in diabetic rats decreased significantly in diabetic rats treated with fenugreek oil. Diabetic rats treated with fenugreek oil restored almost...
47 citations
TL;DR: Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC50 value of AlbizIA lebBeck was found to be 85 μg/ml.
Abstract: Background and aim: The major groups of phytonutrients found in plants include polyphenols, flavonoids, terpenes, amines, etc., all of which are observed to have potential anti-allergic activity. In this study, we evaluated the anti-allergic activity of the standardized extract of Albizia lebbeck with respect to the catechin, a polyphenolic phytomarker.Material and methods: The percentage of catechin in the ethanolic extract was found to be 14.72 mg/g. We administered Albizia lebbeck (50–300 mg/kg) and 50 mg/kg of catechin to mice to evaluate the mast cell stabilization and estimation of histamine elevation in the plasma.Results and conclusion: Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC50 value of Albizia lebbeck was found to be 85 μg/ml. This inhibitory potential of catechin from Albizia lebbeck is perhaps due to modulation of two important effector’s functions, histamine release and cytokine expression of antig...
45 citations
TL;DR: It is suggested that bladder cancer patients develop Th2 dominant status with deficient type 1 immune response that shows tendency to reversal following therapy.
Abstract: Combination therapy with intravesical bacillus Calmette-Guerin (BCG) plus interferon-alpha2b (IFN-alpha2b) for superficial transitional cell carcinoma (TCC) seems to be immune-dependent and activation of Th1 immune response is required for clinical efficacy. The present study evaluates circulating serum cytokine profiles (Th1/Th2 cytokines IFN-gamma, IL-2 TNF-alpha, IL-4, IL-6 and IL-10) in 41 bladder cancer patients prior to transurethral resection of tumor (TURBT) (pre-therapy), and following intravesical combination immunotherapy (post-therapy) and their association with recurrence. Mean levels of IL-2 and TNF-alpha were significantly reduced while IL-4, IL-6 and IL-10 were significantly enhanced in pre-therapy samples as compared to controls. Mean levels of IFN-gamma, IL-2 and TNF-alpha were significantly increased while IL-4 and IL-10 were significantly reduced in patients after instillation of combination immunotherapy. These findings suggest that bladder cancer patients develop Th2 dominant status with deficient type 1 immune response that shows tendency to reversal following therapy.
43 citations
TL;DR: The notion that neither LcS nor BbY exacerbates autoimmune disease is supported, as both strains were administered starting in infancy (two weeks old) and continued until the end of the experiment.
Abstract: To evaluate the safety of two probiotic bacterial strains, Lactobacillus casei strain Shirota (LcS) and Bifidobacterium breve strain Yakult (BbY), these probiotics were orally administered to Lewis rats with experimental autoimmune encephalomyelitis (EAE), the experimental model of human multiple sclerosis. We examined three experimental designs by combining different antigen types and probiotic administration periods: (1) EAE was induced with a homogenate of guinea pig spinal cord as the sensitizing antigen, and LcS was orally administered from one week before this sensitization until the end of the experiment; (2) EAE was induced using guinea pig originated myelin basic protein (MBP) as the sensitizing antigen, and LcS was orally administered from one week before this sensitization to the end of the experiment; (3) EAE was induced using guinea pig MBP as the sensitizing antigen, and the probiotic strains (LcS and BbY) were administered starting in infancy (two weeks old) and continued until the end of t...
TL;DR: With respect to the role of PGs in the induction of inflammation, they can be effective mediators in the pathophysiology of MS and use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in MS.
Abstract: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, axonal loss, and gliosis. The inflammatory lesions are manifested by a large infiltration and a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, and microglia, as well as a broad range of cytokines, chemokines, antibodies, complement, and other toxic substances. Prostaglandins (PGs) are arachidonic acid-derived autacoids that have a role in the modulation of many physiological systems including the CNS, respiratory, cardiovascular, gastrointestinal, genitourinary, endocrine, and immune systems. PG production is associated with inflammation, a major feature in MS that is characterized by the loss of myelinating oligodendrocytes in the CNS. With respect to the role of PGs in the induction of inflammation, they can be effective mediators in the pathophysiology of MS. Thus use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in MS. In this review, we try to clarify the role of PGs in immunopathology and treatment of MS.
TL;DR: There was a significant negative correlation between the CD4+ cell percentage and blood lead levels and length of exposure and this data highlight the adverse effect of lead on immune cells which may have serious consequences for those with chronic exposure to lead.
Abstract: Lead is a common environmental pollutant which has adverse effects on the immune system. We studied frequency of peripheral blood populations of CD4, CD8, and CD56 expressing cells and presence of activation marker (CD25) and CD45 isoforms by flow cytometry. Among 59 lead-exposed individuals (26 three-wheeler drivers, 33 battery workers) and 21 healthy controls, blood lead levels were 6.7 +/- 4.5 microg/dL, 132 +/- 103 microg/dL, and 4.5 +/- 2.0 microg/dL, respectively. The percentage of CD4(+) cells was significantly lower (P < 0.001) and of CD45RA(+) cells higher (P < 0.05) in both lead-exposed groups as compared to controls. There was a significant negative correlation between the CD4(+) cell percentage and blood lead levels and length of exposure. Our data highlight the adverse effect of lead on immune cells which may have serious consequences for those with chronic exposure to lead.
TL;DR: It is demonstrated that SLAK inhibits the production of NO, PGE2, TNF-α, and IL-1β in LPS-stimulated macrophages and possibly occurs by inhibiting iNOS and COX-2 expression via the inactivation of NF-κB pathway.
Abstract: Objective: Members of the Artemisia genus (Astraceae) are important medicinal plants throughout the world. Here, we prepared a sesquiterpene lactone fraction from Artemisia khorassanica (SLAK) and evaluated its effect on inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and nuclear factor-κB (NF-κB) activity.Methods: The effects of SLAK on lipopolysaccharide (LPS)-induced NO, prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production was evaluated in mouse macrophage J774A.1 cells. Moreover, we evaluated SLAK modulation of iNOS and COX-2 enzyme expression by western blot analysis.Results: Our data revealed that SLAK (10–100 μg/mL), in a dose-dependent manner, inhibits NO, PGE2, TNF-α, and IL-1β production induced by LPS in the J774A.1 cells. These data were consistent with the modulation of iNOS and COX-2 expressions. It was also showed that SLAK suppresses the iNOS and COX-2 enzyme expression through the inhibition of NF-κB activity.Conclusio...
TL;DR: The deleterious effects of aflatoxin could be overcome or, at least, diminished by the addition of sorbents, and both HSCAS and TM at the level of 5 g/kg contaminated diet resulted in a significant improvement in all immunological parameters—in lymphocyte, immunoglobulin profile, T-cells sub-types and pro-inflammatory cytokines as well as the mineral status and the biochemical parameters.
Abstract: Background and aim: Previously we reported that hydrated sodium calcium aluminosilicate (HSCAS) and Tunisian Montmorillonite (TM) had an ability to sorb aflatoxins with a high affinity. Addition of these compounds to feedstuffs contaminated with aflatoxins has shown protective effects against the development of aflatoxicosis in farm and laboratory animals. The objective of the current study was to compare the efficiency of HSCAS and the TM in respect to the protection against immuntoxicological effects of aflatoxins in rats.Materials and methods: Animals fed an aflatoxin-contaminated diet (2.5 mg/kg diet) showed a significant decrease in all hematological parameters, cholesterol, triglycerides, cholinesterase, total protein, albumin, zinc and copper concentrations.Results: Such feeding significantly increased createnine, bilirubin, urea nitrogen, alkaline phosphatase and transaminases concentrations. The immunological results showed a significant decrease in lymphocytes of the total white blood cells, imm...
TL;DR: ZnO appears to have an adjuvant effect on the immune system, especially Th2 but not Th1 immune responses, as well as proinflammatory cytokine IL-17 from a new lineage of effector Th cells.
Abstract: Background and aim: We investigated the effect of zinc oxide (ZnO) on Th1 and Th2 immune responses in mice.Material and methods: Mice were intraperitoneally administered with ovalbumin (OVA) with or without varying doses of ZnO (day 0). On day 21, anti-OVA IgG, IgG2a, IgG1, and IgE antibodies in sera, OVA-specific proliferative responses of spleen cells, and production of Th1 cytokines including IFN-γ as well as Th2 cytokines such as IL-4 and IL-5 were measured.Results: The results showed that administration of OVA with ZnO was followed by greater increases in anti-OVA IgG and the antigen-specific splenocyte proliferation compared to that of OVA alone. The production of anti-OVA IgG1 and IgE and secretion of IL-4 and IL-5 were markedly enhanced by ZnO. The enhancing effect of ZnO on these Th2 responses was as strong as aluminium hydroxide (Alum) that was widely used as an adjuvant. In contrast, treatment with OVA plus ZnO failed to affect production of anti-OVA IgG2a as well as IFN-γ. It was also observed...
TL;DR: In the elderly the comorbidities and correlated multiple regime therapy cause an increased incidence of ADRs, thus suggesting a careful management of therapeutics regimens by means of educational campaigns for patients and guidelines for doctors finalized to avoid excessive drug prescription.
Abstract: The use of medications could be responsible of both side effects and adverse drug reaction (ADR). Identifying risk factors could improve the possibility of avoiding severe reactions in old people. We investigated the prevalence of unpredictable drug adverse reactions among patients admitted to the emergency departments (EDs) of three large Italian hospitals in the period 2005–2008. Clinical characteristics and demographics were carefully recorded in a dedicated database. The assessment of the drug reactions was carried out by an allergist after the first emergency evaluation. Over the considered period, 56,031 patients were admitted at the ED, 2644 (21.2%) of which for ADR. Out of those patients, 55 (2.1%) were identified as unpredictable ADRs. In 96% of the cases the clinical presentation was cutaneous and antibiotics were the most frequently responsible drugs. Patients over 65 years accounted for 37% of the reactions. In those patients the multiple drug regimens were significantly more frequent, as well...
TL;DR: An overview of innovative approaches to target LVs to cells of the immune system is provided and it is clear that each strategy is of enormous value but ultimately combining these approaches may help reduce the effects of off-target expression and improve the efficiency and saftey of LVs for gene therapy.
Abstract: Lentiviral vectors (LVs) are efficient gene delivery vehicles suitable for delivering long-term transgene expression in various cell types. Engineering LVs to have the capacity to transduce specific cell types is of great interest to advance the translation of LVs toward the clinic. Here we provide an overview of innovative approaches to target LVs to cells of the immune system. In this overview we distinguish between two types of LV targeting strategies: (i) targeting of the vectors to specific cells by LV surface modifications, and (ii) targeting at the level of transgene transcription by insertion of tissue-specific promoters to drive transgene expression. It is clear that each strategy is of enormous value but ultimately combining these approaches may help reduce the effects of off-target expression and improve the efficiency and saftey of LVs for gene therapy.
TL;DR: Results suggest that G. littoralis is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis and may have therapeutic potential in a variety of immune-related cutaneous diseases.
Abstract: Glehnia littoralis (Umbelliferae) is a traditional medicine used in Korea, China, and Japan to treat the immune-related diseases. However, its anti-inflammatory activities and mechanisms remain to be defined. We investigated the effects of 70% ethanolic extract from G. littoralis (GLE) on skin inflammation in mice. Production of proinflammatory cytokines (IL-1β and TNF-α), activation of myeloperoxidase (MPO), and histological indicators were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability tests. GLE treatment at 200 mg/kg inhibited topical edema in the mouse ear, leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated MPO activity, and several histopathological indicators. Furthermore, GLE effectively reduced inflammatory damage induced by chronic TPA exposure and significantly inhibited the vascular permeability induced by acetic acid in mice. These results suggest that G. littoralis is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis and may have therapeutic potential in a variety of immune-related cutaneous diseases.
TL;DR: Antiallergic effect of Anemarrhena asphodeloides may be due to those of its steroidal constituents, and that of timosaponin AIII may be activated by using intestinal microflora.
Abstract: To investigate the antiallergic effect of the rhizome of Anemarrhena asphodeloides (AA, family Liliaceae), which was found to inhibit the mouse passive cutaneous anaphylaxis (PCA) reaction induced by the antigen-immunoglobulin E (IgE) complex in preliminary experiments, main steroidal saponins, timosaponins AIII, BIII, and D, were isolated and their inhibitory effects against PCA reaction and scratching behaviors investigated in mice. Oral administration of three main steroidal sapogenins blocked the PCA reaction and scratching behaviors, timosaponin AIII was the most potent. However, intraperitoneal administration of timosaponin AIII showed weak inhibition. To understand its metabolism and antiallergic mechanism, timosaponin AIII was anaerobically incubated with human intestinal microflora to afford a main metabolite, sarsasapogenin. Intraperitoneal administration of sarsasapogenin inhibited allergic reaction more potently than timosaponin AIII. In addition, sarsasapogenin more potently inhibited degranu...
TL;DR: Radish extract was effective for the protection of high dose ZEN-immunotoxication in mice and it could contribute to a solution of the ZEN immunotoxicity in humans and in farm animals.
Abstract: Radish (Raphanus sativus) is a cruciferous plant, rich on flavonoids, isothiocyanates, and phenolic acids. They show anti-inflammatory and immunomodulatory activity both in vitro and in vivo. Isothiocyanates and flavonoids have been reported previously to prevent low-sub-chronic dose of zearalenone (ZEN) causing immunotoxicity. The present study focuses on the amelioration of fusarotoxicosis in Balb/c mice by feeding two concentrations of radish extract. The extract at 15 and 30 mg/kg bw, was evaluated to reduce the deleterious effects in immunological parameters of high subchronic doses of 40 and 80 mg of ZEN/kg bw on modulation of lipopolysaccharide (LPS). ZEN consuming mice showed a “dose-related” decrease in weight gain and in the immune relative weights organs. Moreover, Atrophy and lymphoid depletion were seen in the histopathology of spleen. Ingestion of ZEN at either level had a significant effect on total red blood cell numbers and on their relative number of lymphocytes. Likewise, ZEN alters the...
TL;DR: Oral administration of FGM, prepared from Koshu grape for white wine but not from grapes for red wine, could suppress both phases of type-I allergic responses, and a fraction extractable with acetone was responsible for the suppressive effects of F GM.
Abstract: We investigated the inhibitory effects of fermented grape marc (FGM), lyophilized fine powder of skin, and seeds of Vitis vinifera Koshu grape prepared by fermentation with Lactobacillus plantarum, on type-I allergic responses in mice. Repeated oral administration of FGM, but not non-fermented grape marc (GM), to BALB/c mice primed with ovalbumin (OVA) resulted in a significant reduction of serum IgE levels, compared with those of immunized controls. After OVA challenge, increased numbers of eosinophils in bronchial alveolar lavage fluids (BALF) significantly decreased by treatment with FGM but not with GM. For passive cutaneous anaphylaxis (PCA) reaction, BALB/c mice received intradermal sensitization with anti-OVA IgE serum and were challenged intravenously with OVA containing Evans blue at 24 h after IgE sensitization. Oral administration of FGM at 30 min before OVA challenge significantly suppressed the PCA reaction. On the other hand, Lactobacillus alone and non-fermented GM did not show any suppressive effects. Interestingly, FGM samples prepared from grapes for red wine, such as Negroamaro (rich in resveratrol) or Tannat (rich in oligomeric procyanidin), did not suppress the reaction. These results indicate that oral administration of FGM, prepared from Koshu grape for white wine but not from grapes for red wine, could suppress both phases of type-I allergic responses. A fraction extractable with acetone was responsible for the suppressive effects of FGM.
TL;DR: The pathogenic steps of adhesiogenesis and the therapeutic scenario that evolved over the years to tackle the threat of peritoneal adhesions are illustrated, both in domestic animals and in women.
Abstract: Any peritoneal inflammatory process consequent to infections or surgical injuries may induce abdominal adhesion formation. Peritoneal adhesions are connective laciniae that develop among abdomino-pelvic organs that limit physiologic visceral motion. Consequently, fertility may be impaired, and intestinal obstruction and pelvic pain may develop, mainly in subjects that had undergone gynaecological surgery. This review illustrates the pathogenic steps of adhesiogenesis and the therapeutic scenario that evolved over the years to tackle the threat of peritoneal adhesions, both in domestic animals and in women.
TL;DR: It is suggested that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.
Abstract: Background and aim: Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.
TL;DR: In this paper, Pentoxifylline (PTX) has been proven to be an inhibitor of fMLP-induced neutrophil (PMN) oxidative burst and is thought to function by increasing cAMP and Protein kinase A (PKA).
Abstract: Background and Aim: Pentoxifylline (PTX) has been proven to be an inhibitor of fMLP-induced neutrophil (PMN) oxidative burst and is thought to function by increasing cAMP and Protein kinase A (PKA). We hypothesized that PTX diminishes production of the neutrophil respiratory burst by both PKA-dependent and independent mechanisms.Material and Methods: Human neutrophils were isolated and stimulated with fMLP (1μM) alone or in combination with PTX (2mM). PMN activation was determined by the cytochrome C reduction method in the presence and absence of p38 MAPK (SB203580), ERK (PD98059), and PKA inhibitors (H89). Western blot analysis of Ras, Raf, p38 MAPK, ERK, and Akt was performed in PMNs exposed to fMLP and PTX. Cell membranes were fractionated to measure membrane-associated p47 phox. Treated cells were imaged using confocal microscopy to examine changes in localization of Akt and p47phox.Results: PTX produced a decrease in oxidative burst that was diminished but not abrogated by H89 exposure. The reductio...
TL;DR: PSP-regulated gene expression and cytokine secretion related to TLR signaling pathway in human PBMCs indicates TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the key associated signaling pathways in the immunomodulation of PSP.
Abstract: Context: Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers.Objective: To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs).Methods: cDNA microarray and cytokine antibody array were used to identify differential gene expression profiles and cytokines secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of the key genes and proteins related to Toll-like receptor (TLR) signaling and its downstream pathway was determined by RT-PCR or Western blot.Results: Compared with the control group, PSP up-regulated 22 genes expression (such as IFN-γ, CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signa...
TL;DR: It is suggested that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated immune response against strong antigen like TT and weak antigen like OVA.
Abstract: In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund’s adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-med...
TL;DR: Methanol extract of Phellodendri cortex dose-dependently alleviated LPS-induced acute airway inflammation via decreasing the infiltration of inflammatory cells and the release of inflammatory mediators.
Abstract: Background and aim: The effects of methanol extract of Phellodendri cortex on acute airway inflammation induced by intranasal administration of lipopolysaccharide (LPS, 300μg/kg) were investigated in female BALB/c mice.Materials and methods: At 2 h after LPS exposure, mice were treated orally with methanol extract of Phellodendri cortex (100, 200 and 400 mg/kg). At the end of this study, bronchoalveolar lavage fluids (BALF) were collected and number of total cells, macrophages and neutrophils, protein concentration were analyzed. Tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP-2), IL-10 levels and nitric oxide (NO) production in BALF were also determined.Results: Methanol extract of Phellodendri cortex dose-dependently alleviated LPS-induced acute airway inflammation via decreasing the infiltration of inflammatory cells and the release of inflammatory mediators.Conclusion: The relief of airway inflammation provides a possible therapeutic application of Phellodendri cortex for the...
TL;DR: An epidemiological study of allergic manifestations in the elderly conducted in all consecutive patients referred to an Allergology Unit over a three-month period at the beginning of 2008 showed that 15% belonged to the elderly population and among these, 51.8 % were suffering from an allergic reaction to drugs.
Abstract: Recent years have shown a progressive increase of allergic disease in the elderly population worldwide. Naturally, this phenomenon has coincided with attempts to guarantee the best possible quality of life for this age group. As a result, diseases that were previously overlooked are attracting ever greater attention. An epidemiological study of allergic manifestations in the elderly conducted in all consecutive patients referred to an Allergology Unit over a three-month period at the beginning of 2008 showed that 15% belonged to the elderly population and among these, 51.8 % were suffering from an allergic reaction to drugs. Skin manifestations, including both urticaria and eczema, accounted for 71.4% of cases but only in 13.8% of these patients was there a diagnosis of an allergic reaction made and the allergen responsible individuated. Rhinitis was present in 16.8 % of the patients and food allergy in 8 %. Certainly, age-induced modifications in the immunological system can be responsible for allergic reactions. In fact, non specific immunity components such as the production of mucus or a reduced function of the T- and IL-2 cells can induce the onset of symptoms referable to allergic disease. Further studies are ongoing to gain a better understanding of the pathogenic mechanisms that could justify the development in the elderly population of a cytokine phenotype that is more prone to develop allergic manifestations, and to assess the true incidence of respiratory, food and drug allergies in this stage of life.
TL;DR: The results suggest that CVE may be useful in improving the immune function through utilization of a protein-energy malnutrition (PEM) diet.
Abstract: The objective of this study was to investigate the effects of hot water extracts of Chlorella vulgaris (CVE) on a deteriorated immune function through utilization of a protein-energy malnutrition (PEM) diet. Unicellular algae, C. vulgaris, were used as biological response modifier. PEM is associated with decreased host immune defense. Male C57BL/6J mice, initially four weeks old, were fed for 8 days with standard diet or a PEM diet. Mice in the PEM diet group were orally administered 0.1 g/kg and 0.15 g/kg of CVE for the following week. Nutritional parameters such as the total protein, albumin, glucose, and interferon γ (IFN-γ) were increased in blood serum of the CVE-treated group compared with the non-treated group. The mononuclear cell numbers from spleen, superficial, and mesenteric lymph node were reduced in mice fed with PEM diet, but numbers from the spleen and superficial lymph node were increased by the CVE (0.1 and 0.15 g/kg) treatment. We also investigated the effect of CVE on the production of cytokines in human T-cell line, MOLT-4 cells, and primary cultured splenocytes. The CVE treatment significantly increased the production of both interleukin (IL)-2 and IL-4 compared with the media control, but did not affect the production of IFN-γ. These results suggest that CVE may be useful in improving the immune function.