VARIATION IN THE EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS RNA AND CYTOKINE MESSENGER-RNA IN RECTAL MUCOSA DURING THE PROGRESSION OF INFECTION

Previous studies demonstrated that mucosal HIV p24 antigen content varied during the progression of HIV infection. In this study, expression of HIV RNA and mRNA of selected cytokines was examined in rectal mucosa from HIV-infected individuals. Rectal biopsies from 27 subjects were studied: 7 with CD4 counts > 500/mm(3) (early), 11 with CD4 < 500 (intermediate), and 9 with AIDS (late), plus 4 HIV-seronegative controls. RNA in situ hybridization was performed using S-35-labeled riboprobes of HIV, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, INF-alpha, IFN-gamma, and TGF-beta. HIV RNA was detected more frequently in the intermediate group than in the other groups (p < 0.005). Cytokine mRNA expression also varied during disease progression. The expression of IFN-alpha, IFN-gamma, and TGF-beta mRNA was most prevalent early in the disease; peak expression of lL-4, IL-5, IL-6, and IL-10 was seen during the intermediate stage, and peak expression of TNF-alpha and IL-1 beta mRNA were seen in AIDS patients. HIV RNA and cytokine mRNA expression vary during HIV disease progression. HIV RNA expression is greatest in the intermediate stage of the disease. The pattern of cytokine mRNA expression suggests predominant cell-mediated immunity under basal conditions and early in the disease, generalized cytokine activation in its middle phase, and proinflammatory cytokine activation in AIDS patients. Cytokine modulation of HIV expression in rectal mucosa in vivo may occur and have pathogenic importance.