Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases

Abstract

Isoprinosine (IPS) is a new anti-viral agent which appears to have immunomodulatory activities which include its ability to enhance the in vitro blastogenic responses of normal lymphocytes to mitogens. The present study compares the effects of IPS on the in vitro immune functions of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients with its effects on PBMC from normal controls. Each mitogen (Con A, PHA or PWM) was used at its optimal concentration with a range of IPS concentrations (0-25 micrograms/ml). PHA-induced blastogenesis by PBMC from all three groups was enhanced by IPS at or above 5 micrograms/ml. The Con A-induced responses of SLE lymphocytes were significantly enhanced over controls by IPS (P less than 0.02 at 5 micrograms/ml) while those of RA lymphocytes were not. IPS had little effect on PWM-induced blastogenesis by RA lymphocytes but did enhance the blastogenic responses of SLE lymphocytes (P less than 0.01 at 5 micrograms/ml). In contrast, the characteristically high immunoglobulin synthesis by SLE lymphocytes was decreased by IPS. The mechanism responsible for these effects is not known but IL-2 production by patient lymphocytes in vitro which was low for both RA (P less than 0.01) and SLE (P less than 0.02) increased significantly (P less than 0.05) when SLE lymphocytes were cultured with IPS. These data identify IPS as an agent for the study of aberrant immune regulation in autoimmune diseases and suggest that it may have potential therapeutic value in SLE.