[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.

[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.