M. Hamza

Cytokine profile in Behçet's disease patients. Relationship with disease activity.

Objective : To analyse proinflammatory Th1 and Th2 cytokines in patients with Behçets disease (BD) in relation to disease activity. Methods : Forty-five BD patients (25 in active stage) were investigated with ELISA for estimation of cytokines levels. Furthermore, cytokines intracellular synthesis (IL-4 and IFN- n ) of CD4 + T cells was studied. Results : Active and in remission BD patients showed increased serum levels of Th1 (IFN- n, IL-12) and Th2 (IL-4, IL-6 and IL-10) cytokines. Active BD was characterized by a higher increase of IL-6, IL-10 and a striking increase of IL-17, IL-18 and IFN- n, compared to remission BD. Upon in vitro stimulation, the percentages of CD4 + T cells containing IFN- n and CD40L were higher in active BD compared to healthy controls. Conclusion : Our results suggest that the microenvironment of CD4 + T cells in active BD may induce the production of more cells committed to Th1 than in BD patients in remission and healthy controls.

VEGF and mRNA VEGF expression in CSF from Behçet's disease with neurological involvement

Vascular endothelial growth factor (VEGF) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. Several studies have indicated that VEGF-A (VEGF) may play a role in the pathogenesis of neurological inflammatory diseases. To assess the role of VEGF in patients with Behçets disease with neurological involvement, VEGF was measured in the cerebrospinal fluid (CSF) of 32 patients compared to a group of 12 patients with noninflammatory neurological diseases (NIND) and 14 patients with multiple sclerosis (MS). We have also studied the expression of mRNA-VEGF (VEGF-A) in CSF and in peripheral blood mononuclear cells. The mean VEGF(CSF) was significantly increased in neuro-BD and MS patients compared to NIND patients. There was an association between neuro-BD-VEGF(CSF), and leukocyte count. A significant correlation was also observed between neuro-BD-VEGF(CSF) and CSF(%CD4) cells. As a measure of the integrity of the blood-brain barrier Q(albumin) was found correlated to VEGF(CSF). VEGF mRNA was significantly increased in neuro-BD patients compared to NIND patients. These results indicate that, VEGF may be associated with the increased percentages of CD4 cell subpopulation. The role of VEGF is within the inflammatory cascade in the mediation of blood-brain barrier disruption and not specific to Behçets.

Interleukin-6 in peripheral blood and inflammatory sites in Behçet's disease

Interleukin-6, a potent pro-inflammatory cytokine, might be involved in Behçets disease (BD) pathological pathways. We investigated IL-6 levels in sera and synovial fluids collected from BD patients. The IL-6 production was also studied in vivo, by measuring its activity in culture supernatants of PBMC and alveolar macrophages, stimulated or not with LPS. The patients with BD were compared to RA patients and healthy controls. High IL-6 levels were observed in sera, synovial fluid and LPS stimulated PBMC supernatants, from active BD patients, similar to those of RA patients. Alveolar macrophages production of IL-6 was significantly elevated in two active BD patients with an interstitial pneumonia, when compared to controls. These elevated levels of IL-6 suggest its involvement in the inflammatory sites of BD, which may be related to the progression of the acute lesions, at least in the joints and in the lungs.

Antibodies to herpes simplex virus in patients with Behçet's disease

Infectious agents had been incriminated in the pathogenesis of Behcets disease (BD) especially herpes simplex virus type 1 (HVS-1). This hypothesis is supported by many findings. Hybridization studies showed complementary RNA to HSV-1 DNA in the mononuclear cells from patients with BD (1). The phytohaemagglutinin-transformed lymphocytes from patients with BD were unable to support the growth of HSV-1 (2). A proliferative response of HSV-l-stimulated CD4 cells from patients with BD was observed (3). Increased IgG anti HSV-1 antibodies were found in sera and the PEG material from patients with BD in England (4). In this work we study the levels of HSV-1 serum antibodies in Tunisian patients.