BackgroundAdamantiades-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.MethodsThe 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.ResultsOur 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.ConclusionThis 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.

SummaryBeçget syndrome is a multisystem disorder characterized by ocular, mucocutaneous, articular, gastrointestinal and neurologic abnormalities. We report here an unusual case of Beçget syndrome, characterized by the importance of the thrombotic events(7 phlebitis of both legs and resection of two toes). Additional manifestations of the Beçget syndrome occurred only 10 years after the first thrombotic episode. The oldest daugther of the propositus and his brother suffered also from thrombophlebitis; this familial history of thrombosis led to the performance of a haemostatic study. A congenital protein S deficiency was found in the propositus and in three of his children. Normal protein S levels were found in nine unrelated patients with Beçget syndrome. Thus this observation suggests that, when thrombotic manifestations are the first and major symptom of Beçget syndrom, an additional cause of thrombosis has to be investigated.

Behçet'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.

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