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Background: Oral aphthosis is one of the major manifestations of Behçet’s disease (BD), a chronic, multisystemic vasculitis. BD etio-pathogenicity related to oral health lack. Objective: This study investigated the possible relationships between poor oral hygiene, oral activity, disease severity and saliva’s Interleukin (IL)-32, IL-6, IL-10 and nitric oxide (NO) levels in Behçet’s patients to determine their role in disease prognosis and their potential therapeutic interest. Method: Fifty-six patients with BD (22 orally active; 34 orally inactive) and 31 healthy subjects have been included in our study. Salivary levels of IL-32, IL-6, and IL-10 were measured using ELISA, while NO levels were assessed by modified Griess’s method. Oral health status and disease severity scores were recorded for each participant. Kruskal-Wallis test and Spearman’s test were performed for statistical analyses. Results: We observed that the tested molecules were increased in BD patients compared to healthy controls (p˂0.05). Moreover, only IL-32 levels were associated with oral activity in patients (p˂0.05). Interestingly, the disease severity score was noted to be correlated positively and significantly with both IL-32 saliva levels (p˂0.01) and plaque index (p˂0.05) in BD patients. Furthermore, IL-32 levels were correlated with plaque index (p˂0.0001). Conclusion: Our results suggest that IL-32, IL- 6, IL-10 and NO were increased in saliva during BD. Our study indicated that IL-32 was associated with the genesis of oral ulcers in response to dental plaque. Ultimately, salivary IL-32 may serve as a prognostic biomarker and a possible therapeutic target for managing Behçet’s disease severity.

Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of Dimethylfumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into 7 experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund’s adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500 µL of Dimethylfumarate at 100mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On days 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.

Primary Sjogren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C16H14O4), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS. For this purpose, peripheral blood mononuclear cells isolated from pSS patients and healthy controls were cultured with different concentrations of cardamonin. Cytokine levels were measured by ELISA and NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence staining. Our results suggest that cardamonin inhibits TNF-α, IL-6 and NO production and downregulates iNOS expression and NF-κB activation. Collectively, our results highlight the ex vivo immunomodulatory effects of cardamonin on pro-inflammatory cytokine production and NO pathway in pSS patients. Therefore, cardamonin is a potential candidate for controlling inflammation during pSS.

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.

Uveitis is one of the major diagnostic criteria of Behcet'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 C. 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). 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.

Behçet's disease (BD) is a multisystem disease, which shares some features with other diseases belonging to the autoinflammatory disorders panel. Recent studies have postulated that IL-1β/Caspase-1 may play a cardinal role in autoinflammatory diseases. In this study, we aimed to (i) elucidate the mechanism underlying the involvement of xanthine oxidase (XO) and Uric Acid (UA) in BD (ii) study the direct effects of UA and XO inhibitor "Allopurinol" on nitric oxide (NO) and caspase-1-mediated IL-1β release in peripheral blood mononuclear cells (PBMCs) of BD patients. In this context, plasma of BD patients and healthy controls (HC) were used to measure XO activity, UA, advanced oxidized proteins products (AOPP) and NO levels. In Addition, PBMCs of BD patients and HC were treated or not with either UA or Allopurinol. Then we quantified NO and IL-1β levels, and Caspase-1 Activity in the supernatants and lysates of PBMCs, respectively. We showed that plasma levels of XO activity, UA, AOPP and NO are significantly increased in BD patients compared to those of HC. Interestingly, a significant positive correlation between XO and UA was observed in BD patients. Additionally, while UA has markedly increased NO, IL-1β, and Caspase-1 activity levels in PBMCs of BD patients, Allopurinol has exerted an immunomodulatory effect resulting in reduced NO, IL-1β and Caspase-1 levels in PBMCs of BD patients particularly during the active stages. Collectively, our results indicate a potential clinical use of XO as a tool for assessing BD activity, and suggest that the in-vitro immunomodulatory effect of Allopurinol may have a promising therapeutic value in BD management.

Behcet’s disease is a multisystem disease. It stands at the crossroad between the autoimmunity and auto-inflammatory disorders. In this study, we sought to address a relationship that might exist between interleukin-1β (IL-1β) and the oxidants/antioxidants markers in Behcet’s patients. Behcet’s disease patients (n = 78: active stage, n = 28; inactive stage, n = 50) and 41 healthy controls have been included in our study. In this context, we investigated the plasma levels of IL-1β and the nitrosative/oxidative markers: nitric oxide (NO), advanced oxidative protein products (AOPP) and fatty acids peroxidation-malondialdehyde (MDA). The antioxidant system was assessed by measuring the plasma level of superoxide dismutase (SOD) activity. The Mann-Whitney’s U and Pearson’s correlation tests were used for statistical analyses. Our case-control study showed that patients in active stage displayed higher plasma levels of IL-1β, NO, AOPP and MDA versus healthy controls and patients in inactive stage. Patients in active stage showed significantly lower SOD levels related to patients in inactive stage and healthy controls respectively, whereas patients in inactive stage showed statistically insignificant SOD level versus healthy controls. Correlation studies showed a significant positive correlation between IL-1β and AOPP, IL-1β and NO, and negative correlation between IL-1β and SOD among Behcet’s disease patients. In addition, we showed positive correlation between AOPP and NO, AOPP and MDA and negative correlation between NO and SOD, AOPP and SOD in Behcet’s disease patients. Interestingly, our study revealed that IL-1β levels increased and correlated with an imbalance of oxidants/antioxidants system, especially during active stage of Behcet disease. Collectively, our study indicates a possible link between IL-1β production and nitrosative/oxidative markers during Behcet’s disease. Exploiting this relationship might provide valuable outputs in the follow-up and prognosis of Behcet’s disease with a potential therapeutic value.

In this study, we evaluated the preventive and curative effects of ethanolic extract of Propolis (EEP) during α-Tropomyosin-induced uveitis in an experimental model using Wistar rats, through the regulation of inducible nitric oxide synthase (NOS2) and arginase-1. In this context, rats received daily injection of EEP (100 mg/kg) for 5 days prior to immunization or for 9 days commencing 5 days post immunization with α-Tropomyosin extract, then were sacrificed at day 14. Histological examination, NOS2, arginase-1, and nuclear factor-κB (NF-κB) expression were evaluated in the retinas. Plasmatic production of nitric oxide (NO), urea, IL-4, and TNF-α was assessed. We have found that treatment with EEP substantially reduced the retinal histological damages induced by α-Tropomyosin. In the same context, a significant decrease of NO and TNF-α levels was noticed. Interestingly, EEP down-modulated NOS2 and NF-κB expression in retina. Also, an increase in urea and IL-4 levels was concomitant to an up-modulation of arginase-1 expression. Hence, it appears that EEP attenuated retinal damages through the induction of Th2 response and the inhibition of NF-κB/NOS2 pathway.

Behcet’s disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients. For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess’ method in naive-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients. Our results indicate that IL-18 and nitrite levels were higher in naive-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations. Collectively, our results suggest that concomitant high production of IL-18 and NO in naive-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency.

Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.

Behcet's disease (BD) is an inflammatory multisystemic disorder associated with orogenital ulcers, uveitis and skin lesions with unpredictable episodes of exacerbations and remissions. Even though several immunological and environmental factors contribute to BD progression, its ethiopathogenesis remains uncertain and elusive. Considered as one of the potent environmental factors that can increase prevalence of some autoimmune and inflammatory disorders, vitamin D deficiency has been linked to several diseases as BD. The aim of this study is to assess vitamin D status in Algerian BD patients and its relationship with disease activity. Immunomodulatory effect of this vitamin on nitric oxide (NO), inflammatory mediator, was also undertaken. Serum 25(OH) vitamin D levels were measured in healthy controls (HC), active and inactive BD patients with an electrochemiluminescence method. After treatment of HCs' and patients' peripheral blood mononuclear cells with different concentrations of vitamin D3, NO production was evaluated with Griess method, while inducible nitric oxide synthase (iNOS) and NF-κB expression with immunofluorescence test. A high decrease of vitamin D levels was noted in active BD patients compared to those of inactive stage and HC. However, a higher NO production was observed during active stage of BD compared to inactive one. In inactive BD, vitamin D levels correlates negatively with NO. Interestingly, vitamin D3 inhibits ex vivo NO production, iNOS and NF-κB expression in BD patients. In conclusion, vitamin D deficiency was associated with active BD. This vitamin down-modulates NO production in BD patients, suggesting that it may be considered as promising therapy modulating inflammation during BD.

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.

Resume Introduction Durant l’inflammation intraoculaire, il a ete rapporte par plusieurs auteurs une production importante de monoxyde d’azote (NO) avec la formation de peroxynitrite. Dans une etude anterieure, nous avions montre l’effet cytotoxique des nitrites et des nitrates, derives metaboliques stables du NO, sur les differents tissus formant les tuniques oculaires avec des degres de sensibilite variables. La presente etude vise a situer l’effet du peroxynitrite, sur la totalite des explants oculaires bovins en culture. Methodes Des yeux sains bovins, obtenus immediatement apres enucleation, ont ete disseques et les explants oculaires ont ete preleves de la partie anterieure et de la partie posterieure puis mis en culture dans du milieu minimum essentiel de Eagle (DMEM) additionne de serum de veau fœtal, de 2 mM de L glutamine et d’antibiotiques. Les cultures ont ete traitees avec le 3-morpholino-sydonimine N-ethyl-carbamide (SIN-1) (molecule generatrice de NO et de l’anion superoxyde O 2 .− ) a des concentrations allant de 100 a 500 μM pendant 24 heures. Apres incubation, les explants ont ete fixes dans du formol tamponne a 10 % et une etude histologique a ete entreprise. Resultats La majorite des structures a montre des alterations d’ordre tissulaire et cellulaire apres incubation avec le donateur de peroxynitrite. Les differents tissus analyses ont repondu differemment selon les concentrations utilisees. Ces observations traduisent une sensibilite variable et dependante de la concentration. Les epitheliums (cornee, proces ciliaires et iris) ont montre une haute sensibilite en comparaison a la sclerotique qui a developpe une plus grande resistance. Conclusion Nos resultats dans leur ensemble indiquent que le peroxynitrite induit des effets deleteres sur les structures oculaires in vitro. Cet effet est proportionnel a la concentration utilisee. Nos resultats corroborent ceux rapportes par d’autres equipes et suggerent le role du peroxynitrite produit du NO dans les lesions oculaires observees durant les uveites.

Resume Introduction L’uveite est une inflammation intraoculaire constituant l’une des manifestations les plus severes de la maladie de Behcet. L’antigene S (Ag S), proteine retinienne hautement conservee, a ete fortement incriminee dans la physiopathologie de cette affection. Elle est utilisee chez differents modeles experimentaux afin d’induire l’uveite auto-immune experimentale (UAE), modele in vivo de l’uveite humaine telle que l’uveite Behcet. La production du monoxyde d’azote (NO) a ete rapportee par plusieurs travaux au cours de cette affection, en particulier par notre equipe. Materiels et methodes Les objectifs vises par notre etude ont porte sur la mise au point d’un modele experimental d’uveite Behcet chez le rat Wistar, induite par l’Ag S. Ce dernier a ete isole a partir de retines bovines, par gel filtration sur Sephadex G-200. Les animaux ont recu 10 μg de l’Ag S par voie sous-cutanee. Afin de situer l’implication du NO, l’evolution de la production plasmatique de ses derives stables, par la methode de Griess modifiee, a ete poursuivie sur ce modele aux septieme, 14e et 21e jours de l’immunisation. Une etude histologique du tissu retinien a ete realisee en parallele en vue de la mise en evidence des effets deleteres de l’Ag S en relation avec la production du NO. Resultats Nos resultats ont montre une augmentation significative des taux du NO in vivo chez les rats Wistar traites avec l’Ag S en comparaison avec les temoins, avec une difference de production selon les phases symptomatiques de l’UAE. Par ailleurs, l’Ag S a induit des effets deleteres notables sur le tissu retinien des rats Wistar traites. Conclusion Une production maximale de NO a ete notee durant la phase precedant ces alterations. Le NO constitue un bio-marqueur de mauvais pronostic au cours de l’UAE. Ainsi, le stress oxydatif pourrait etre considere comme l’etape pathologique initiale menant a la destruction des photorecepteurs. Ces donnees pourraient etre utiles dans la reflexion a la mise en place d’une strategie dans l’etablissement d’un diagnostic precoce chez les patients atteints d’uveite de Behcet.

Resume Introduction L’uveite est une inflammation intraoculaire pouvant atteindre les differentes structures de l’œil. Elle est caracterisee par une production importante de monoxyde d’azote, estimee par la mesure de ses derives metaboliques stables finaux, les nitrites et les nitrates. L’effet cytotoxique de ces derniers sur la retine bovine in vitro a ete montre dans une etude anterieure. L’objectif de notre etude etait d’evaluer leur effet sur la totalite des explants oculaires bovins en culture. Methodes Apres examen clinique, des yeux sains bovins ont ete obtenus immediatement apres enucleation et ont ete transportes au laboratoire a une temperature de +4 °C. Apres dissection, des explants oculaires de la partie anterieure et de la partie posterieure de l’œil ont ete mis en culture dans du DMEM supplemente de 10 % de serum de veau fœtal, 2 mM de glutamine, 100 UI/ml de penicilline et de 100 UI/ml de streptomycine. Les cultures ont ete traitees avec differentes concentrations de nitrites et de nitrates (300-500 μM). Apres un temps d’incubation (24 heures-48 heures), les explants oculaires ont ete fixes dans du formol tamponne a 10 %, et ont fait l’objet d’une etude histologique. Resultats Des alterations tissulaires et cellulaires etaient observees dans toutes les structures oculaires, mais a des degres differents selon la concentration et le temps d’incubation. Les differentes structures oculaires presentaient des sensibilites differentes vis-a-vis de la nature du metabolite et de sa concentration. La sclerotique etait la structure ayant montre le plus de resistance alors que l’epithelium corneen ainsi que celui des proces ciliaires etaient les plus atteints. Conclusion Cette etude montre un effet cytotoxique des nitrites et des nitrates sur les structures oculaires in vitro . Cet effet etait proportionnel a la concentration et au temps d’incubation utilises. Les alterations observees au niveau des differentes structures suggerent l’implication du monoxyde d’azote, a travers ses derives, dans les lesions oculaires observees durant les uveites.

Effet de la corticotherapie sur la production des interleukines 8, 12 et du monoxyde d’azote au cours des uveites Behcet et idiopathique Objectifs : Notre travail porte sur l’etude de l’effet de la corticotherapie sur la production des interleukines 8, 12 et du monoxyde d’azote (NO) au cours des uveites Behcet et idiopathique. Methodes : Le sang peripherique veineux a ete obtenu a partir de 38 patients atteints d’uveite idiopathique active, de 32 patients atteints d’uveite Behcet active avant et pendant la corticotherapie et de 30 sujets sains. Apres la collecte du plasma, les cellules mononucleees du sang peripherique ont ete separees immediatement et mises en culture en presence ou en absence de phytohemagglutinine A (PHA). Les concentrations des interleukines 8 et 12 (IL-8 et IL-12) ont ete mesurees dans le plasma et les surnageants de culture par dosage immuno-enzymatique specifique (ELISA sandwich). Les taux du NO sont estimes par une methode de Griess modifiee. Resultats : Avant therapie, les deux categories de patients ont montre, in vivo et in vitro , une augmentation tres significative des taux des IL-8, IL-12 et du NO chez les patients atteints d’uveite idiopathique et Behcet par comparaison aux sujets sains. Les taux de l’IL-8 et du NO ont montre une diminution significative, in vivo et in vitro , suite a l’administration des corticoides aux deux categories de patients. De meme, in vitro , l’IL-12 a montre une diminution significative apres administration des corticoides au cours des deux pathologies. A l’inverse, les taux plasmatiques d’IL-12 ont significativement diminue au cours de l’uveite idiopathique. Cet effet n’a pas ete observe chez les patients atteints d’uveite Behcet. Conclusion : Nos resultats suggerent l’implication des cytokines : IL-8 et IL-12 et du monoxyde d’azote dans les mecanismes physiopathologiques des uveites idiopathique et Behcet. Chacune de ces molecules a montre une sensibilite specifique a l’action des glucocorticoides refletant des voies de regulations differentes sous l’action de la corticotherapie au cours des deux pathologies. Notre etude indique dans sa globalite que l’IL-8 pourrait servir de marqueur inflammatoire. A l’inverse, l’IL-12 constituerait un marqueur de la reponse immunitaire specifique des phases aigues des uveites.

Introduction: nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is important in host defence against Mycobacterium tuberculosis in animal models. But the presence of high output NO production in human tuberculosis has been controversial. Objective: To investigate nitric oxide expression (NO) in pleural tuberculosis Methods: The serum and pleural fluid NO in the patients with exsudative pleural effusion were analyzed. Results: Of total 151 patients, there were 77 males and average age of patients was 47, 28 ± 19, 5 years. The final diagnosis was tuberculous pleurisy in 84 cases and malignant pleural effusion in 67. The pleural fluid NO level was 68, 46 ± 57, 88 μmol in the tuberculous pleurisy patients and 62, 39 ± 51, 45 μmol in the malignant pleural effusion patients (p Conclusion: NO is not a suitable marker for tuberculous pleuritis because, because it is produced in other pathologies such as neoplasic and inflammatory diseases.

Introduction/but L’uveite est une inflammation intraoculaire qui forme une des plus serieuses expressions du syndrome de Behcet. Le monoxyde d’azote (NO) est une molecule exprimant d’importantes proprietes immuno-inflammatoires. Il est synthetise par les NO synthases (NOS). Dans une etude anterieure, nous avons montre une augmentation de la production du NO endogene dans les uveites Behcet et celles classees « idiopathiques ». L’objectif de la presente etude est de situer le role du monoxyde d’azote (NO) dans la genese des lesions observees in vivo au niveau de la retine durant les uveites et ce, en etudiant l’effet de deux de ses metabolites physiologiquement stables, les nitrites et les nitrates sur les retines de bœuf in vitro. Materiel et methodes Les retines etaient issues d’yeux de bœuf fraichement enuclees. Elles etaient ensuite mises en culture dans du DMEM a 10 % de serum de veau fœtal en presence des differentes concentrations de nitrites ou de nitrates, pendant 24 heures a 37°C, en atmosphere humide sous 5 % de CO2. Une etude morphologique et histologique etait realisee. Resultats Un effet dose-dependant pour les deux effecteurs etait observe. A partir d’une concentration de 200 μM pour les nitrites et de 250 μM pour les nitrates, un effet toxique et probablement necrotique etait observe, cet effet s’etant traduit par des lesions tissulaires et cellulaires. Conclusion Les nitrites et a moindre degre les nitrates, deux metabolites physiologiquement stables du NO, ont un effet deletere sur les retines en culture. De ce fait, le NO produit au cours des processus inflammatoires des uveites pourrait etre implique dans la destruction des retines in vivo.

The aim of the current study is to situate CDs expression (CD3+, CD4+, CD8+) and their relationship with IFNγ and NO production in Algerian patients with Behçet disease (n = 34 ). Our results revealed an elevated expression of T cells markers tested in patients in active stage of the disease in relation to IFNγ and NO increase levels. Most interestingly, we noted that CD4+/CD8+ expression correlated with IFNγ and NO production in active stage. In contrast, we observed a decrease of these mediators in inactive stage. Collectively, our results indicate a dependent relation between these parameters and inflammatory response associated with the evolutionary stage of the disease.

Aim and Methods. In this study, we evaluated NOS and arginase activities and their regulation during Behçet disease, a systemic chronic inflammatory disorder with uncertain etiology. The peripheral blood mononuclear cells of 36 patients and 15 control samples (PBMC) were cultured in either RPMI 1640, MEM, or DMEM complemented with 10% of FBS and antibiotics. Cultures were performed with or without the control or patients plasma. Subsequent treatment contained anticytokines (IL-6, TGF-β), a mitogenic effector (PHA), or NOS modulators (L-NMMA, BH4). Culture supernatants were harvested after 24 h of incubation. NO and urea measurements were, respectively, performed by modified Griess and Berthelot methods.Results. Higher urea levels were found in patients’ plasma compared to the control’s (P< 0.05). NOS modulators induced inverted production profiles for NO and urea (P< 0.05). Their results differed depending on the clinical findings (P< 0.05). It was also found that cytokine neutralization induced different response profiles in patients as opposed to control cultures (P< 0.05).Conclusion. Our results suggest that arginases can compete with NOS2 for L-arginine during Behçet disease. Both enzymes are regulated by environmental cytokines and substrate availability. Furthermore, it seems that NOS/arginase balance is dependent on clinical expression.

Uveitis represents one of the major diagnostic criteria in Behcet'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 Behcet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behcet'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.

Pterygium is a common ocular surface disease observed in humans. This disease is frequent in Algeria. Chronic UV exposure is an extensively recognized etiological factor in the pathogenesis of Pterygium. This hypothesis is sustained by epidemiological and histopathological data in relation to the UV injured skin. The mechanisms of pterygium development are poorly understood. Some findings indicated the implication of a genetic factor, anti-apoptotic mechanisms, and immunological mechanisms in the development of the disease. In our study, we report in vivo IL-17A, IL-6 and NO production, in tears and in sera from algerian patients. Cytokines and NO production are strongly related to the NO synthase2, NF- κ B, Bcl2 expression and inflammatory infiltrates in pterygia biopsies. Collectively, our results indicate the involvement of TH17/NO inflammatory pathways in primary pterygia pathogenesis.

Background Adamantiades-Behçet's disease (ABD) is a chronic multisystemic inflammation with unknown pathophysiology. This disorder is associated with a dysregulation of the cytokine network that hyperactivates neutrophils and macrophages. In this study, we investigate the modulatory effects of flavonoïd compounds extracted from Algerian medicinal plant Artemisia herba alba on Th1 and Th2 cytokines and nitric oxide production. Methods The modulatory effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production by peripheral blood mononuclear cells isolated from Algerian ABD patients and healthy controls were respectively measured by means of ELISA assays and Griess modified method. Results Our results show that flavonoïds significantly reduce the production of interleukin-12, the key effector of T helper 1 (Th1) cells and nitric oxide in a dose-dependent manner in Adamantiades-Behçet's disease. In contrast, the production of IL-4, the key marker of Th2 cells was increased. Conclusion This study suggests that in vitro supplementation with flavonoïds extracted from Artemisia herba alba could have potential immuno-modulatory effects characterised by a down-regulation and up-regulation of Th1 and Th2 cytokines, respectively. Moreover, flavonoïds may prevent nitric oxide induced damages.

Uveitis is one of the major manifestations of Behçet Disease, a systemic inflammatory vasculitis. Our aim is to investigate in vivo and in vitro production of interferon (IFN)-γ and nitric oxide (NO) during Behçet uveitis (BU). Moreover, we evaluated the implication of IFN-γ and interleukin (IL)-10 in the regulation of NO production in vitro. Cytokines' concentrations were measured by ELISA, and NO levels were assessed by modified Griess's method. Our results showed that patients with active disease had significant elevation of IFN-γ and NO concentrations in both plasma and peripheral blood mononuclear cell culture supernatants compared with controls (P0.01) or to patients with inactive disease (P0.05). Further, IFN-γ induced significantly higher production of NO in cell culture supernatants, whereas IL-10 significantly reduced it (P0.05). In conclusion, the elevated levels of IFN-γ in vivo and in vitro in patients with BU reflect the implication of this cytokine in the disease physiopathology. These results suggest that IFN-γ, through the induction of NO synthase 2 and the production of NO, is implicated in the genesis of the inflammatory process during active BU; whereas IL-10 seems to have protective properties.

Summary 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.

Hydatidosis is a widely endemic helminthic disease vectored in human by the larval stage of the metacestode Echinococcus granulosus. It is characterized by the long-term coexistence of chronic infection with detectable humoral and cellular responses against the macroparasite. Previous studies demonstrated interferon-gamma (IFN-gamma) and nitric oxide (NO) production (in vivo and in vitro) during hydatidosis. In this study, we tested the hypothesis that NO production after IFN-gamma induction may constitute a host defense against E. granulosus. We also investigated the IFN-gamma effect on protoscolices (larval form of the parasite) viability in coculture with hydatid patients' peripheral blood mononuclear cells (PBMC). PBMCs from hydatic patients incubated with IFN-gamma (100 U/mL) alone are effective in the killing of protoscolices. This scolicidal activity is concomitant with elevation of nitrite levels. NO release and cytotoxic activity are inhibited by N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the NO pathway and increased by L-arginine, an NO precursor, and tetrahydrobiopterin (BH4), a nitric oxide synthase (NOS) cofactor. Our results indicate that IFN-gamma mediated iNOS induction as one of host defense mechanism against human E. granulosus infection.

Behcet disease (BD) is a systemic chronic inflammatory disorder frequent in Algeria. As Behcet disease is considered as a vasculitis, we assessed the levels of circulating B cells by flow cytometry, antibodies (IgM, IgA, IgG) by nephelometry and auto-antibodies (ANCA, APLs) by Luminex in 70 patients with BD and 20 control subjects. The obtained results were analyzed by Mann Witney U test. We observed a significant increased B cells and antibodies levels in comparison to control group ( p 0.01 ). Patients showed different profile according to the clinical data (activity: p 0.05 , clinical expression: p 0.01 ). Autoantibodies indicated different profiles with no differences with controls in ANCA levels ( p > 0.05). In contrast, anti-phospholipids were higher during BD with aCL (anticardiolipins) revealing a significant difference ( p r = 0.760, p p

Introduction Le diagnostic de la tuberculose pleurale par les methodes conventionnelles est difficile. Objectifs Evaluer la performance et l’interet clinique du QuantiFERON-TB Gold InTube (QFT-GIT) dans le diagnostic de la pleuresie tuberculeuse. Patients et methodes Le QFT-GIT a ete teste dans le serum et dans le liquide pleural sur un recrutement prospectif de 158 patients immunocompetents, ayant presente un epanchement pleural exsudatif. Resultats Les patients ont ete repartis en 2 groupes selon le diagnostic retenu : – groupe 1 : 84 pleuresies tuberculeuses prouvees aux examens complementaires classiques ou fortement suspectes de tuberculose par la presence d’arguments de presomption (notion de contage, IDR a la tuberculine positive et presence d’un granulome tuberculoide sans necrose caseeuse a la biopsie pleurale) ; – groupe 2 : 74 pleuresies non tuberculeuses dont 67 d’origine maligne, 5 secondaires a une maladie systemique, et 2 d’origine inflammatoire. Nos resultats ont montre, une haute sensibilite pleurale du QFT-GIT (95,5 %) par rapport a la sensibilite serique (86,1 %). En revanche, la specificite serique (84,5 %) est plus elevee que la specificite pleurale. En conclusion, le QFT-GIT teste dans le serum et dans la plevre apparait dans notre etude comme un test utile pour le diagnostic des pleuresies tuberculeuses, bien que sa specificite pleurale soit modeste. En attendant sa validation, comme un test standard dans le diagnostic de la pleuresie tuberculeuse, il serait necessaire de l’utiliser devant un tableau clinique evocateur de la pleuresie tuberculeuse, dont les resultats des examens classiques sont negatifs, et en cas de contre-indication a la biopsie pleurale.

Behcet disease (BD) is a systemic inflammatory disorder with uncertain etiology. This disease is frequent in Algeria. Several studies reported the presence of auto-antibodies during Behcet disease. In this study, we evaluated the production of IL-6 and BAFF during Behcet disease and their effect on B cell responses in vitro . 26 patients with BD during active ( n = 16) or inactive ( n = 10) stage were included in our study. Plasma were obtained from patients and controls peripheral blood. BAFF and IL-6 were assessed by ELISA tests while total IgG, IgA and IgM were measured by nephelometry. Control Peripheral B lymphocytes (PBL) were purified and cultured in RPMI 1640 complemented by 10% FBS and antibiotics in presence or absence or patients’ plasma (20%). After 24 h, cells’ activation and/or differentiation markers were analyzed by flow cytometry (CD19, CD5, IgD, CD38). The comparison of the groups tested was performed by Mann–Whitney U test for soluble factors while markers’ expression was compared by Student T test. Our results showed a significant IL-6 and BAFF production increase during BD in comparison to controls ( p p p

Introduction Behcet disease (BD) is an inflammatory, chronic, systemic affection with uncertain etiology. In previous works, we showed that BD is characterized by a Th1/Th2 cytokines profile. However, recent works showed the presence of Th17/Treg responses. In this study, we measured the IL-6, IL-17 and TGF- β levels in vivo during BD and their effect on in vitro production of two inflammatory metabolic products: NO and urea. Methods PBMC were separated from peripheral blood samples of 43 patients with BD and 23 controls. Then, cells were cultured in RPMI 1640 complemented with 5% FBS, 20% patient’s plasma, 2 mM of glutamine and antibiotics during 24 h in presence or absence of either anti-IL-6, anti-TGF- β (1/20) or IL-17 (20 pg/ml). IL-6, TGF- β and IL-17 were measure by ELISA sandwich; NO was measured by a modified Griess method and urea was measured by a modified Berthelot method. Statistical analysis was performed using ANOVA method. Results We observed a significant increase in IL-6 and TGF- β concentrations in patients’ plasma when compared to controls ( p p In vitro IL-6 and/or TGF- β neutralization also showed different results depending on the clinical manifestations. Furthermore, IL-17 addition induced two major responses. It reduced significantly NO and urea production in ocular and vascular impairments while it increase their production during nervous and rheumatoid manifestations ( p Conclusion In conclusion, our results showed heterogeneous presence of IL-17/Th17 responses during BD. Th1 responses seems to be the main physiopathological mechanism implicated in the disease’s acute phases.