MOLECULAR ANALYSIS OF DECREASED INTERLEUKIN-12 PRODUCTION IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS

Human immunodeficiency virus (HIV) disease is associated with loss of type 1 responses, including interleukin (IL)-12 production. The dramat ic drop in p70 production seen at early stages of disease was found no t to be associated with a similarly decreased p40 mRNA expression. p35 mRNA expression was more extensively reduced than p40 mRNA expression at these early stages, Monocytes infected in vitro with HIV displayed decreased p35 expression and p70 production, suggesting that such dec reased IL-12 expression may contribute to reduced IL-12 production in HIV-positive patients' cells. In addition, treatment of cells with IL- 10 increased IL-10 mRNA expression and decreased p40 expression in bot h MV-positive and -negative cells, while neutralization of IL-10 incre ased p40 mRNA levels. These observations, together with the observed h yperproduction of IL-10 in HIV-positive patients, may explain the dysr egulation of IL-12 production seen in HIV disease.