OBJECTIVE: IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during pulmonary Behçet's disease (BD), we have explored the capacity of IL-18 to induce the expression of IFN-gamma. METHODS: We studied bronchoalveolar lavage (BAL) from 12 patients with BD, 10 patients with silicosis as the control disease and 10 BAL from healthy subjects. BAL fluid, and BAL fluid cell cultures were investigated for IL-18 estimation by ELISA. Analysis of IL-18 and IFN-gamma gene expression was carried out before and after LPS stimulation. RESULTS: BD patients had significantly elevated levels of IL-18 in BAL fluid compared with control disease and healthy subjects. Induction of IFN-gamma and IL-18 were observed from BD-BAL fluid cells both spontaneously and after LPS stimulation, at higher levels compared to silicosis patients and healthy subjects (HC). Spontaneously only BD BAL cells expressed IL-18 mRNA and IFN-gamma mRNA. Forty-eight hours after LPS stimulation IL-18 mRNA and IFN-gamma mRNA were observed in BD, silicosis and HC cells. Recombinant IL-18 induced IFN-gamma production in BD- BAL fluid cells. CONCLUSION: Administration of IL-18 induced greater IFN-gamma production in BD-BAL fluid cells, than in normal BAL fluid cells. Our data indicate that IL-18 up-regulation is a feature of BD and suggest that IL-18 and IFN-gamma may contribute to the local inflammatory response in BD.

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Circulating soluble CD28 in patients with Behçet's disease: relationship to clinical manifestations.

OBJECTIVE: This study evaluates the presence of serum soluble CD28 (sCD28) in Behçet's disease (BD) and its relationship with clinical manifestations. METHODS: Soluble CD28 concentration was determined by ELISA in 120 patients with BD (80 patients in active stage), 60 patients with rheumatoid arthritis (RA) and 60 healthy subjects. RESULTS: Concentrations of sCD28 were significantly higher in patients with BD and RA than in healthy subjects. Patients with active BD expressed the highest level of sCD28 in serum. Soluble CD28 exhibited a drastic increase in active BD patients, compared to BD in remission. Soluble CD28 concentrations were higher in patients with active BD patients having vasculitis. Significant positive correlation was observed in a longitudinal study of 15 BD patients, between sCD28 and C-reactive protein. CONCLUSION: Our study suggests that fluctuations of sCD28 in BD reflects disease activity and should be assessed in evaluating disease activity.

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CD4+CD25+ regulatory T cells in patients with Behçet's disease.

OBJECTIVE: To investigate whether the CD4+CD25+ regulatory T cell (Treg) population, which plays important role in autoimmune diseases is related to the pathophysiology of Behçet's disease (BD). METHODS: Forty-two patients with BD (20 patients in active disease) fulfilling the criteria of the International Study Group of BD. Twenty age-matched healthy controls were studied. We analyzed CD4+CD25+/high T cells and the mRNA expression of Foxp3, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and transforming growth factor beta (TGF-beta) in BD. We have studied the ability of CD4+CD25+ (Treg) to regulate proliferation of CD4+CD25- T cells during active BD stage. RESULTS: Active BD patients had significantly higher CD4+CD25+/high T cells, as compared with BD in the remission stage, and healthy controls. There was no significant differences in the CD4+ CD25+/high T cells expression between healthy controls and remission BD. In active BD, mRNA for Forkhead box p3 (Foxp3) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) were highly expressed when compared to remission BD and healthy controls. There was no differences in the mRNA expression for TGF-beta in active BD, remission BD and healthy controls. Functionally, CD4+CD25+/high T cells in active BD were impaired in their proliferative responses and could suppress the proliferation of their CD4+CD25- counterparts. CONCLUSION: These data demonstrate that CD4+CD25+ Treg cells, with the potential to regulate suppression of effector T cells, were increased in the peripheral circulation of active BD patients. The role of CD4+CD25+/high T cells in the regulatory process of the inflammation in active BD, could be taken in account.

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