POSSIBLE ROLE OF INTERLEUKIN-10 (IL-10) AND CD40 LIGAND EXPRESSION INTHE PATHOGENESIS OF HYPERGAMMAGLOBULINEMIA IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - MODULATION OF IL-10 AND IG PRODUCTION AFTER INTRAVENOUS IG INFUSION

The mechanisms leading to polyclonal hypergammaglobulinemia in patient s with human immunodeficiency virus (HIV) infection are not well under stood. In light of the important role of interleukin-10 (IL-10) and th e interaction between CD40 and CD40 ligand in the normal regulation of B-lymphocyte function and Ig production, we examined these parameters in 24 HIV-infected patients. Both plasma IL-10 levels and the percent age of CD4(+) and CD8(+) lymphocytes expressing CD40 ligand were signi ficantly higher in the patients than in the 10 blood donor controls. S erum IgG correlated positively with circulating IL-10 levels and the p ercentage of CD4(+) lymphocytes expressing CD40 ligand. Furthermore, a single bolus infusion of intravenous Ig (0.4 g/kg) in 8 HIV-infected patients caused a further increase in IL-10 levels in plasma and an in crease in both IL-10 and IgG production in peripheral blood mononuclea r cell cultures. In another patient group (Wegener's granulomatosis) r eceiving a single bolus infusion of intravenous Ig, a similar increase in plasma IL-10 levels was found, suggesting that this may be a gener al effect of intravenous Ig. In patients with HIV infection, our data suggest that a vicious cycle may be operative where high endogenous Ig levels may enhance IL-10 production that, in turn, leads to higher Ig production. (C) 1998 by The American Society of Hematology.