Production of IL-8 and the other cytokines by T cell clones established from the ocular fluid of patients with Behçet's disease

Abstract

Behçet's disease is a systemic inflammatory disease immunologically characterized by the infiltration of CD₄⁺T cells and polymorphonuclear cells in the affected tissues, including the eye. Despite extensive studies, neither the etiology nor the pathogenic mechanism of Behçet's disease has been clarified. Production of cytokines by T cell clones (TCC) from the ocular fluid (18 CD₃⁺CD₄⁺CD8 clones and 4 CD₃⁺CD₄^-CD8⁺ clones) and peripheral blood mononuclear cells (PBMC) (16 CD₃⁺CD₄⁺CD8^- clones) of two patients with uveitis associated with Behçet's disease was investigated to understand better the immunopathology of the disease. The level of IL-8 spontaneously produced by TCC from the ocular fluid (mean: 659 pg/ml) or PBMC (536 pg/ml) of the patients was significantly higher (p<0.005, and p<0.05, respectively) than that by TCC (18 CD₃⁺CD₄^+-CD8⁺ clones) and 4 CD₃⁺CD₄^-CD8⁺ clones) from PBMC of healthy donors (241 pg/ml). As for the other cytokines, IL-Iα, IL-2, IL-6, IL-10, and TNF-α were produced at low but detectable amounts by the majority of TCC from the ocular fluid of patients with Behçet's disease; IL-3, IFN-Y, and GM-CSF were produced by some of TCC at low amounts; and IL-4 was not produced by any TCC tested. IL-8 production by TCC from the ocular fluid was further up-regulated upon stimulatation with PHA, but was suppressed by FK506 and hydrocortisone, though not by diclofenac sodium. Colchicine rather increased IL-8 production by these TCC. These results suggest that T cells in both the affected tissues and PBMC play an important role in the pathogenesis of uveitis associated with Behçet's disease through IL-8 and probably the other cytokines.

Key Words:

• IL-8
• Behçet's diseas
• uveitis
• ocular fluid
• T cell clones