Probiotic bacteria lactobacillus and bifidobacterium attenuate inflammation in dextran sulfate sodium-induced experimental colitis in mice.

It is widely accepted that inflammatory Bowel disease (IBD) arises from a dysregulated mucosal immune response to the enteric microbiota in the gut of a genetically susceptible individual. No definitive therapies are available for this inflammatory disorder. Therefore it became imperative to develop new strategies for treating this disease. Probiotics have emerged as a potential new therapeutic strategy for IBD, however their exact mechanisms of action is still poorly defined. In this study, we address the potential effect of a probiotic cocktail (Ultrabiotique®) composed of four live bacterial strains (L. acidophilus, L. plantarum, B. lactis and B.breve) to promote recovery from acute colitis. Probiotic was given to mice by oral gavage after the onset of colitis and the establishment of dextran sulfate sodium (DSS)-induced intestinal injury. Clinical parameters were monitored daily, histological scores of colitis and the production of nitric oxide (NO) and interferon-γ (IFN-γ) were determined. In addition, TLR4, NF-κB and iNOS colonic expression were examined. Probiotic treatment ameliorated clinical symptoms and histological scores. NO and IFN-γ production in plasma were decreased by probiotic. These results were associated with reduced TLR4, iNOS and NF-кB expression in colonic tissue. In conclusion, probiotic exerted anti-inflammatory effects and contributed to a rapid recovery of DSS-induced acute colitis.

[The 869C>T And 915G>C Polymorphisms of TGF-ß1 and Type 1 Diabetic Retinopathy in the Algerian Population]. / Polymorphismes 869C> T et 915 G>C du TGF-ß1 dans la rétinopathie du diabète de type 1 chez la population algérienne.

INTRODUCTION: Diabetic retinopathy (DR) is characterized by chronic low-grade inflammation in which the effects of genetic factors is well established. The objective of our study is to explore an association of the 869C>T and 915G>C polymorphisms of the TGF-ß1 gene with type 1 diabetic retinopathy in the Algerian population. PATIENTS AND METHODS: A case-control study was carried out in which the SNPs 869C>T and 915G>C of the TGF-ß1 gene were analysed by the PCR-SSP technique. We compared the distribution of allelic and genotypic frequencies between patients with and without retinopathy and looked for an association between these polymorphisms and certain clinical characteristics of and risk factors for diabetic retinopathy. RESULTS: A significant increase in the frequencies of the C allele (P=0.03) and GG genotype (P=0.007) of the 915 G>C polymorphism were found, respectively, in patients without and with retinopathy. However, no significant difference was found for allelic and genotypic frequencies of the 869C>T SNP (all P>0.05) or associations between genotypes and clinical characteristics or risk factors for DR. CONCLUSION: Our preliminary results suggest that the C allele of the 915 G>C polymorphism of TGF-ß1 is protective against type 1 diabetic retinopathy in the Algerian population, while the GG genotype could confer susceptibility to it.

[Cytokine profile in human hydatidosis: possible role in the immunosurveillance of patients infected with Echinococcus granulosus]. / Etude du profil cytokinique de patients atteints d'hydatidose: une possible application en matière d'immunosurveillance.

Hydatidosis is a severe parasitic disease caused by infection with metacestode of the tapeworms Echinococcus granulosus. In human, the larval forms develop into large cysts especially in the liver, lung and brain. Our aim in this study was to investigate Th1 and Th2 cytokines production in hydatid disease in order to evaluate implication of Th1/Th2 ratio in the evolution of pathology according to the cystic localization, clinical stage and clinical evolution. Interferon-gamma (IFN-gamma), interleukine-12 (Il-12), interleukine-16 (Il-16), interleukine-18 (Il-18), interleukine-4 (Il-4), interleukine-5 (Il-5), interleukine-10 (Il-10) and interleukine-13 (Il-13) production is determined in sera from hydatid Algerian patients (n = 177) with liver, lung, liver and lung associated, spleen, kidney, osseo, heart and multiples hydatid cyst and in sera from patients with clinical complications (calcified liver cysts; infected lung cysts; vomique lung cysts and patients who relapsed) and according clinical stage (before surgical extirpation of the cyst and after surgical extirpation of the cyst). Cytokines are evaluated by enzyme-linked immunosorbent Kits (ELISA Immunotech). The coexistence of elevated activities of IFN-gamma, Il-12, Il-16, Il-18, Il-4, Il-5, Il-10, and Il-13 is observed in most of sera from hydatid patients. In contrast, healthy controls showed minor levels. These results support Th1 and Th2 cell subsets activation in human hydatidosis. The comparison of Th1/Th2 production shows that the induction of these mediators is related to the cystic localization, the clinical stage and clinical evolution. Collectively, our data indicates that Th1 cytokines are related to the protective immunity, in contrast Th2 cytokines are responsible to the susceptibility to disease and associated with chronicle stage, clinical complications and secondary locations.

[T-786C endothelial nitric oxide gene polymorphism and type 1 diabetic retinopathy in the Algerian population]. / Polymorphisme T-786C de l'eNOS dans la rétinopathie du diabète de type 1 chez la population algérienne.

INTRODUCTION: Diabetic retinopathy (DR) results from interactions between genetic and environmental factors. We were interested in the endothelial nitric oxide gene (eNOS), given the involvement of this enzyme in functional alterations in the retinal microvasculature in diabetes. The goal of our study was to assess the association of T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism with diabetic retinopathy in the Algerian population. PATIENTS AND METHODS: Our study enrolled 110 patients with and without DR. All subjects were genotyped for the T786C eNOS polymorphism using the PCR-RFLP method. We also investigated the association between this polymorphism and certain clinical and laboratory characteristics of patients with DR. RESULTS: A significant increase in the frequency of the CC genotype is noted in subjects without DR (P=0.03). We also report a significant increase in the frequencies of the TT+TC genotypes in individuals with DR (P=0.03). However, the association between the different genotypes and clinical or laboratory profiles in patients with DR reveals that the NO level is lower in subjects carrying the TT genotype (P=0.039). CONCLUSION: Our preliminary results suggest that the CC genotype could confer protection from type 1 diabetic retinopathy in the Algerian population, while the T allele seems to confer susceptibility.

Clinical variables and ethnicity may influenced by polymorphism of CAT -262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications.

The latest studies in Algeria show that the frequency of type 1 diabetes (T1D) without complications is lower than that with complications and represents a significant burden in terms of cost and treatment. For this reason, we are interested in uncomplicated type1 diabetes and risk factors that are related to polymorphisms of antioxidant enzymes in order to prevent its complications. A total of 260 blood samples of young Algerian adults were examined. The genotypic analysis of Catalase gene (CAT -262C/T, rs1001179) and the superoxide dismutase gene (MnSOD 47C/T, rs4880) was performed by real-time PCR using TaqMan technology. The genotypic distribution of the CAT -262C/T promoter gene's polymorphism showed a significant difference between control and T1D patients for the CC genotype (p = 0.009; OR = 0.30) and for the T allele (p = 0.002; OR = 2.82). In addition, the genotypic distribution of the MnSOD 47C/T gene showed an association with T1D for the CT genotype (p = 0.040; OR = 2.37). Our results revealed that polymorphisms of CAT and MnSOD may be associated with physiopathology causing the onset of T1D. Our data, suggest that the genotypic frequencies of these SNPs appear to be influenced by clinical variables and by the Arab-Berber ethnic origin of the Algerian population.

Local pro-inflammatory cytokine and nitric oxide responses are elevated in patients with pterygium.

Pterygium is a common ocular surface disease observed in humans. Chronic ultraviolet (UV) exposure is extensively recognized as an aetiological factor in the pathogenesis of this disease. This hypothesis is sustained by epidemiological and histopathological data in relation to UV injured skin. Although some findings have indicated that genetic factors, anti-apoptotic and immunological mechanisms are involved in the pathogenesis of pterygium, the mechanism by which it develops remains poorly understood. In this study, we analysed the in vivo production of IL-17A, IL-6, IL-10 and nitric oxide (NO) in the tears and sera from Algerian patients. Interestingly, we observed that IL-6, IL-17A and NO production in the tears and sera of all patients was strongly associated with inflammatory infiltration, NOS2, NF-κB and Bcl2 expression in pterygia biopsies. Collectively, our results indicate a relationship between local inflammation and anti-apoptotic processes in pterygium disease, leading to both tissue damage and enhanced cellular proliferation.

Alterations in interferon-gamma and nitric oxide levels in human echinococcosis.

Human cystic hydatid disease is characterized by the long-term coexistence of Echinococcus granulosus and its host without effective rejection of the parasite. This parasitic helminth infection currently constitutes a major health problem in Algeria. We investigated interferon-gamma (IFN-gamma) and nitrite (NO2-) production in PBMC culture 2 supernatants from Algerian patients (n = 35), stimulated by a major antigen (antigen 5). Nitrite was also observed in 74 sera and 28 cyst fluids of patients carrying cysts in different locations. In addition, we report the detection of Nitric Oxide Synthase-2 (NOS2) in liver biopsies of patients (n = 8) by an immunochemical method using human NOS2 antibody. In vivo nitrite levels in host sera and cyst biological fluid point to a tight relation between host response and macro-parasite effects. Our in vitro results indicate a correlation between nitrite and IFN-gamma production in PBMC culture supernatants. Furthermore, by immunohistochemistry NOS2 expression was observed in hepatocytes and Küpffer cells from hydatid patients. Collectively, our data imply NO production in host defense against the extracellular parasite, probably in response to an IFN-gamma activating signal. Concomitant enhanced levels of IFN-gamma and nitrite represent useful indicators of the clinical aggressiveness of hydatidosis.

[Influence of steroid hormones on the production of two inflammatory markers, IL-12 and nitric oxide, in Behçet's disease]. / Influence des hormones stéroïdes sur la production de deux marqueurs inflammatoires, l'IL-12 et le monoxyde d'azote, au cours de la maladie de Behçet.

Uveitis is one of the major diagnostic criteria of Behçet's disease (BD), a chronic systemic inflammatory pathology with an uncertain etiology. Since uveitis is more frequent in male patients, we assessed the level and the effect of sex hormones on inflammatory responses during BD. Peripheral blood was taken from 19 patients with BD and 20 healthy subjects. Estradiol, testosterone and cortisol were measured in plasma by ELISA. Circulating mononuclear cells (PBMC) were obtained on gradient density and cultured with or without the three hormones for 24h at 37 ÌŠC. IL-12 and nitric oxide (NO) were measured in vivo and ex vivo by ELISA and a modified Griess method, respectively. We confirmed the significantly higher in vivo and in vitro levels of NO and IL-12 in BD in comparison to controls (P<0.05). We also found that circulating cortisol was lower in BD while sex hormones did not show any significant difference between the groups (P>0.05). In vitro, NO was reduced by estradiol and cortisol and increased by testosterone in both sexes. In contrast, while IL-12 production showed the same production profile as NO in women, estradiol and cortisol failed to reduce IL-12 levels in men. Our results may explain in part the differences observed between men and women in disease clinical expression. In fact, male patients seem to have defective IL-12 down-regulation by estradiol and cortisol that increases Th1 immune responses. This may be implicated in the severe expression of BD in men.

In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy.

Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process.

Relationship among circulating interferon, tumor necrosis factor-alpha, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis.

Human hydatidosis is a parasitic disease vectored by the larval stage cestode Echinoccocus granulosus. It constitutes a major health problem in North Africa. We investigated the production of circulating interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Algerian patients with liver, lung, or ocular hydatidosis. In all, 101 serum samples from these patients with analyzed. Immunoreactivity and cytokine activities were undetectable in sera from ocular hydatidosis patients. However, we observed the presence of IFN (a mixture of IFN-alpha, IFN-beta, and IFN-gamma, range 32-500 U/ml), TNF-alpha (range 32-100 U/ml), and IL-6 (range 32-500 U/ml) in all patients who had liver or lung cysts or both and displayed immunoreactivity against parasitic antigen (antigen 5). After surgical removal of the cysts, serum cytokine levels declined rapidly and were undetectable at 30 days. IFN and IL-6 activity was undetectable in sera from two liver hydatidosis patients who relapsed and did not display any immune response against parasitic antigen. These results suggest that in liver and lung hydatidosis, cytokine production contributes to the host defense mechanism against the extracellular parasite.

Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-gamma levels.

Human hydatidosis is characterized by a prolonged coexistence of parasite (Echinococcus granulosus) and host without effective rejection. The basis of the immune response of the patient is poorly understood. Previously, we reported the presence of IFN, TNF-alpha and IL-6 activities in the serum of patients with liver and lung hydatidosis. In the present work, we have investigated the production of nitrite (NO2-) in the serum of hydatidic patients carrying hepatic and pulmonary cysts (range 36-300 microM). Our present data show a correlation between the production of nitrite + nitrate (NO2- + NO3-) and that of circulating cytokines IFN and IL-6. In relapsing patients who did not produce IFN and IL-6, the observed serum NO2- concentrations were low (range 10-37.2 microM), as compared to those detected in patients before surgery. Induction of NO synthase in leukocytes from hydatidic patients was induced by stimulating these cells with a specific parasitic antigen, Antigen-5, as assessed by the increased levels of NO3- + NO2- in the range of 60-85 microM for patients with liver hydatidosis, as compared to the 20-25 microM detected in healthy controls. Collectively, our data indicate that NO2- + NO3- levels correlate with IFN levels and immunoreactivity, and overall suggest that IFN-gamma and nitric oxide production together play a role in the host defense mechanisms in human hydatidosis.

[Effects of peroxynitrite derived from nitric oxide on cultured bovine ocular explants]. / Effets du peroxynitrite dérivé du monoxyde d'azote sur des explants oculaires bovins en culture.

INTRODUCTION: Several studies have reported a significant production of nitric oxide (NO) with peroxynitrite formation in the setting of intraocular inflammation. In a previous study, we showed the cytotoxic effect of nitrites and nitrates, stable metabolites of NO, on the various tissues forming the layers of the eye, with variable degrees of tissue sensitivity. This study aims to investigate the effect of peroxynitrite on whole ocular bovine explants in culture. METHODS: Healthy ocular bovine eyes, obtained immediately upon enucleation, were dissected and samples were taken from the anterior and posterior segments, and then cultured in DMEM supplemented with 10% fetal bovine serum, 2mM L-glutamine and antibiotics. Cultures were treated with 3-morpholino-sydonimin N-ethyl-carbamide (SIN-1) (molecule which produces NO and superoxide anion O(2)(.-)) at varying concentrations (100 to 500 µM) over 24 hours. After incubation, the explants were fixed in 10% buffered formalin, and histological study was performed. RESULTS: Most of the structures showed changes on tissue and cellular levels after incubation with the peroxynitrite donor and various responses depending on the concentration used. These observations reflect variable concentration-dependent tissue sensitivity. The epithelia (cornea, iris and ciliary process) showed high sensitivity in comparison with sclera, which developed greater resistance. CONCLUSION: In all, our results indicate a deleterious effect of peroxynitrite on bovine ocular structures in vitro. This effect is proportional to the concentration used. These results corroborate those reported by other teams and suggest the role of peroxynitrite derived from NO in the ocular lesions observed in the setting of uveitis.

Early involvement of nitric oxide in mechanisms of pathogenesis of experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein (IRBP).

INTRODUCTION: Autoimmune uveitis is a group of HLA-associated inflammatory diseases of the eye, prevalent worldwide, that may cause blindness. It can be limited to the eye, or associated with a systemic syndrome. Furthermore, patients suffering from uveitis exhibit high serum and local nitric oxide (NO) levels as a consequence of cellular responses to immunologically privileged antigens within the eye such as interphotoreceptor retinoid binding protein (IRBP). To investigate NO production kinetics in autoimmune uveitis and its implication in mechanisms of ocular pathogenesis, we first attempted to develop an experimental model of autoimmune uveitis (EAU) on the Wistar rat, using the whole bovine retinal interphotoreceptor matrix extract (IPMe) and isolated IRBP. MATERIAL AND METHODS: Female Wistar rats (n=24) were divided into three experimental groups: "control rats" (n=3) consisting of non-immunized animals, "IRBP-immunized rats" (n=12) and "IPMe-immunized rats" (n=9), which received a subcutaneous injection, respectively, of 13 µg IRBP and 100 µg IPMe emulsified in complete Freund's adjuvant. On days 7, 14 and 21 post immunization, the rats were sacrificed. Nitrites were assessed in plasma and in homogenate of eyes using the Griess reaction. Meanwhile, eyes were collected for histological studies. RESULTS: Our results show the sensitivity of the Wistar strain to both IPMe and IRBP-induced EAU. In fact, we observed histological disorders affecting the retinal tissue in both models of EAU. On the other hand, a significantly increased production of NO in plasma and homogenate of eyes was also observed in comparison to the control group. Moreover, we noted with interest that maximal production of NO occurs prior to the alteration of retinal tissue. CONCLUSION: In summary, our results suggest the early involvement of NO in the mechanisms of pathogenesis of EAU. NO can be considered as a key bio-marker of poor prognosis in ocular autoimmune inflammation.

[Nitric oxide, biomarker of experimental autoimmune uveitis induced by S antigen]. / Le monoxyde d'azote, bio-marqueur de l'uvéite auto-immune expérimentale induite par l'antigène S.

INTRODUCTION: uveitis is an intraocular inflammation and one of the most severe and frequent manifestations of Behçet disease. S antigen (S Ag) is a highly conserved retinal protein implicated in the mechanism of the physiopathology in Behçet disease. This autoantigen is used in different animal models for experimental autoimmune uveitis (EAU) development, particularly in Behçet uveitis. Nitric oxide (NO) production has been reported in this disease by several groups and mainly by our team. MATERIALS AND METHODS: in this study, we investigated the development of Behçet uveitis in an experimental model using the Wistar rat after treatment with S antigen. This antigen was isolated and purified from bovine retina by gel filtration chromatography using Sephadex G-200. The rats were immunized with 10µg of S Ag. We evaluated the changes in nitric oxide metabolite production in plasma using the Griess reaction, during the 7th, 14th, and 21st days post-immunization. Furthermore, deleterious effects by S antigen on retinal tissue were assessed in a histological study. RESULTS: the results showed a significant increase in NO production in Wistar rats treated with S Ag in comparison with controls. We noted with interest that the clinical stages of EAU correlated with NO production. Furthermore, S Ag had several deleterious effects on Wistar rat retina. CONCLUSION: this study indicated in vivo elevation of NO levels, which was observed before retinal tissue damage. Nitric oxide appears to be a good marker for a poor prognosis in this experimental model. Moreover, oxidative stress can be considered the primary step in pathogenesis inducing the destruction of retinal photoreceptors. Collectively, our data could be helpful in the development of strategies for diagnosing patients with Behçet uveitis.

[Deleterious effects of stable nitric oxide derivatives, a uveitis inflammatory marker, on cultured bovine ocular layers]. / Effets délétères des dérivés stables du monoxyde d'azote, marqueur inflammatoire des uvéites, sur les différentes tuniques de l'oeil de boeuf en culture.

INTRODUCTION: Uveitis is an intraocular inflammation affecting various eye segments. This disease is characterized by a high level of nitric oxide production. It is estimated via the quantification of its end products: nitrites and nitrates. In a previous study, we showed the cytotoxic effect of these molecules on bovine retina in vitro. In this study, we investigated the effect of these two molecules on cultured ocular explants in vitro. METHODS: After clinical examination, healthy bovine eyes were obtained immediately after enucleation and were transported to the laboratory at +4 degrees C. After dissection, ocular explants from anterior and posterior segments were cultured in DMEM supplemented with 10% of FBS, 2mM glutamine, 100UI penicillin, and 100UI/ml streptomycin. Cultures were treated with either nitrites or nitrates at different concentrations (300-500 microM). After culture incubation (24-48h), ocular explants were fixed in buffered formalin and the histological study was performed. RESULTS: All structures showed structural alterations in relation with culture duration and molecule concentrations. The different structures showed different degrees of sensitivity depending on the type and concentration of the metabolite used. Sclerotic analysis showed very little response to the two molecules, whereas the cornea and ciliary process epithelia showed the highest sensitivity. CONCLUSION: Our results showed a cytotoxic effect of nitrites and nitrates on ocular structures in vitro. This effect was correlated with molecule concentration and duration of exposure. The structural alterations observed suggest that nitric oxide, via its products, is implicated in the ocular lesions observed during uveitis.

[Effect of corticotherapy on interleukin-8 and -12 and nitric oxide production during Behçet and idiopathic uveitis]. / Effet de la corticothérapie sur la production des interleukines 8, 12 et du monoxyde d'azote au cours des uvéites Behçet et idiopathique.

OBJECTIVES: To investigate the effect of corticotherapy on IL-8, IL-12, and nitric oxide (NO) production during idiopathic and Behçet active uveitis. METHODS: Peripheral venous blood was drawn from 70 patients with active uveitis before and during corticotherapy (32 with Behçet uveitis and 38 with idiopathic uveitis) and from 30 controls. Plasma was collected and peripheral blood mononuclear cells were separated immediately and cultured with or without Concanavaline A. IL-8 and IL-12 levels in plasma and culture supernatants were measured by specific enzyme-linked immunosorbent assay (ELISA). Nitric oxide levels were evaluated using a modified Griess method. RESULTS: Before therapy, the two groups of patients showed highly significant elevation of IL-8, IL-12, and NO levels compared to control subjects. During therapy, IL-8 and nitric oxide levels were significantly lower in active idiopathic and Behçet active uveitis both in vivo and in vitro. This effect was correlated with therapy duration. In contrast, while significant reduction of IL-12 levels was observed both in vivo and in vitro in idiopathic active uveitis during therapy, this effect was observed in vitro in Behçet active uveitis but not in vivo. CONCLUSION: Our results suggest that IL-8, IL-12, and NO are involved in the physiopathological mechanisms of idiopathic and Behçet uveitis. These three molecules showed different degrees of sensitivity to the inhibitory effect of corticoids, reflecting their different regulation by corticotherapy during active phases of the two diseases. According to our study, IL-8 can serve as a marker of inflammatory responses, while IL-12 should be used as a marker of the specific immune responses during active uveitis.

[Effect of nitrites and nitrates on bovine retina in vitro]. / Effet des nitrites et des nitrates sur les rétines de boeuf in vitro.

BACKGROUND/AIM: Uveitis is an endocular inflammation that forms one of the most serious manifestations of Behçet disease. Nitric oxide (NO) is a molecule that expresses important immunoinflammatory properties and is produced by NO synthases (NOS). In previous studies, we showed an elevated production of endogenous NO during Behçet's and idiopathic uveitis. These results led us to investigate the effect of nitrites (NO2-) and nitrates (NO3-) (physiologically stable metabolites of NO) on fragments of bovine retina in order to determine the role of nitric oxide (NO) in the genesis of retinal lesions during uveitis. MATERIAL AND METHODS: Retinas were removed from freshly enucleated bovine eyes and cultured in DMEM, 10% CFS in presence of nitrites (NaNO2) or nitrates (NaNO3) at different concentrations. The cultures were processed at 37 degrees C, 5% CO2 in a humidified chamber. Cultured retinas were observed by inverse microscopy and then fixed in formaldehyde. Histological studies were conducted after H & E staining. RESULTS: Cultured retina showed alterations when exposed to concentrations of nitrites and nitrates higher than 200 microM and 250 microM, respectively. These alterations were dose-dependent and affected the cellular and tissular structures. Morphological and histological studies suggested that the toxic effect is apoptotic and/or necrotic for both effectors. CONCLUSION: Our investigations showed that nitrites and nitrates, two physiologically stable metabolites of NO, have a deleterious effect on cultured retina. NO, produced in inflammatory processes during uveitis may be implicated in the genesis of the retinal lesions observed during the exacerbation phase of the disease.

[Production of Th1/Th2 cytokines and nitric oxide in Behçet's uveitis and idiopathic uveitis]. / Production des cytokines Th1/Th2 et du monoxyde d'azote au cours de l'uvéite "Behçet" et de l'uvéite "idiopathique".

INTRODUCTION: The aim of this study was to investigate the role of Th1 (IFN-gamma and IL-12), Th2 (IL-10) cytokines and nitric oxide (NO) in the immunopathologic mechanisms of uveitis related to Behçet's disease and isolated idiopathic uveitis. PATIENTS AND METHOD: This study was conducted on 24 patients with Behçet's syndrome who had active uveitis, ten of whom showed isolated uveitis classified as idiopathic uveitis, and 13 healthy controls. The levels of IFN-gamma, IL-12 and IL-10 in sera and supernatants of PBMC cultures stimulated by PHA were estimated using immunoenzymatic dosage (ELISA sandwich according to the methods recommended by Immunotech France). The production of NO was measured in vivo and in vitro for the same patients using the modified Griess method. RESULTS: The induction of IFN-gamma and IL-12 was higher in the two groups of patients than in the controls (P<0.001). Significant IL-10 levels were recorded in 56.5% of patients with Behçet's disease presenting uveitis versus 30% of patients with idiopathic uveitis. NO production was more pronounced in idiopathic uveitis than in Behçet's syndrome (P<0.02). CONCLUSION: The predominance of the Th1 profile was associated with high production of NO in idiopathic uveitis. A Th1/Th2 profile with a moderated increase in NO production was observed in Behçet's disease. Our data have a clinical impact. The observation of combined Th1/Th2 cytokines and NO elevation in both in vivo an in vitro experiments could have a predictive value in characterizing uveitis associated with Behçet's disease.