Effect of Interleukin 12 onin VitroHIV Type 1 Replication Depends on Clinical Stage

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Abstract
CD8-depleted PBMCs from 20 HIV-1-seropositive donors were incubated in the presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2 or rIL-12 in five of seven asymptomatic subjects and was not induced by either cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced increased detectable p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only in cell lines from 5 symptomatic subjects and then only marginally. In IL-2 containing cultures from subjects with minor symptoms of HIV infection, the mean p24 Ag was 320 ± 217 pg/ml versus 27 ± 6 in IL-12-containing cultures (p = 0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold compared to cultures from this group incubated with only rIL-2 (p = 0.03). Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from subjects who had had a major AIDS infection, although the number of CD4 cells in four of six of those cultures was markedly reduced. IL-4, IFN-γ, and IL-10 production induced by exposure to IL-2 and/or IL-12 were also measured. In CD8-depleted cultures from all infected asymptomatic donors and from some symptomatic donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-γ and IL-10 production. Cytokine-induced production of IL-4, IFN-γ, and IL-10 was greater in cultures from asymptomatic donors than in cultures from symptomatic subjects. Our results suggest that IL-12 immunotherapy may be complicated by enhancement of viral expression in asymptomatic individuals.

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