Lymphokines in autoimmunity: relationship between interleukin-2 and interferon-gamma production in systemic lupus erythematosus

Abstract

Interleukin-2 (IL-2) and interferon (IFN) are potent immunoregulatory factors. Recently, it has been demonstrated that IL-2 production is necessary for IFN-gamma synthesis. Thus, defects in IL-2 production could lead to defects in IFN-gamma production. Indeed, in systemic lupus erythematosus, defects in IFN-gamma and IL-2 production have been noted. To test this hypothesis, IL-2 and IFN-gamma production rates by peripheral blood mononuclear cells PBMC were measured simultaneously after stimulation by concanavalin A (Con A) and phorbol myristic acetate (PMA). IL-2 activity was determined employing HT-2, a cell line with an absolute growth requirement for IL-2. IFN-gamma activity was assessed using a standard viral plaque inhibition assay. IL-2 production in normal controls (n = 6) was 14.7 +/- 9.4 units/ml and in SLE patients (n = 10), 18.0 +/- 10.5 units/ml (P greater than 0.05). IFN-gamma production in controls was 74.7 +/- 43.7 units/ml and in SLE patients, 68.8 +/- 35.4 units/ml (P greater than 0.05). Only one SLE patient, who had moderately active disease, demonstrated defects in IL-2 synthesis (less than 4 units/ml) and IFN-gamma production (16 units/ml). Thus, production of these lymphokines in SLE patients was largely normal in response to Con A-PMA. These results imply that the intrinsic pathways of IFN and IL-2 production are basically normal in most SLE patients although defects in production of these lymphokines can occur. The defects in IL-2 and IFN production in SLE previously reported may be secondary to an impaired cellular response to the selected inducing agent rather than a primary defect in the actual ability to produce these important lymphokines.