Differential expression of interferon gamma by mitogen-stimulated peripheral blood mononuclear cells among Kuwaiti psoriasis patients

Abstract

Most diseases exhibit characteristic profiles of cytokine expression, broadly subdivided into Th1, involving primarily cell-mediated responses, of which Interferon-gamma (INF-gamma), Interleukin-2 (IL-2) and Tumor Necrosis Factor-alpha (TNF-alpha) are hallmarks, and Th2 processes, which often involve activation of the humoral arm of the immune system, resulting in elevated levels of IL-4, IL-5 and IL-10. Psoriasis, a disorder characterized by disfiguring skin lesions and elevated levels of activated CD4+ T helper lymphocytes in both peripheral blood and lesional tissue, exhibits a profile of cytokine expression that includes high levels of TNF-alpha and IFN-gamma, with low IL-5 and IL-10, indicating that immunologically, the pathogenesis of the disease is Th1. In this study, we report the results of an investigation of peripheral blood mononuclear cell cytokine expression among Kuwaiti psoriasis patients; we demonstrated two patterns of IFN-gamma production which may suggest differing pathogeneses. Whole, haparinized blood was donated by 17 patients with active psoriasis and 11 healthy control subject. Mononuclear cells were isolated by density centrifugation and cultured for 3 days in the presence or absence of a mitogen (PHA). Supernatants were assayed for IFN-gamma (a Th1 marker) and IL-10 (a Th2 marker) by enzyme-linked immunoabsorption assay (ELISA). IFN-gamma expression by both PHA-stimulated and unstimulated cultures from psoriatics significantly exceeded that of controls (p < 0.001), whereas no significant differences in IL-10 expression were noted between psoriatic and control subjects. Stimulation indices (cytokine concentration in PHA-stimulated/unstimulated cultures, SI) for psoriatic subjects were significantly higher than those of controls for IFN-gamma (p = 0.000), but not for IL-10. Ratios of SI (SI IFN-gamma/SL IL-10) for the psoriatic subjects also were significantly greater for the psoriatic subjects than for the controls (p = 0.003). However, within the psoriatic group, eight patients failed to show the expected elevation of IFN-gamma/IL-10 ratio as a result of high unstimulated levels of IFN-gamma production. The divergence of IFN-gamma expression within the psoriatic group may indicate two different modes of T lymphocyte activation contributing to the pathogenesis of psoriasis in this study.