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/mm3 (early), 11 with CD4 < 500 (intermediate), and 9 with
AIDS (late), plus 4 HIV-seronegative controls.
RNA in situ hybridization was performed using 35S-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
IL-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.