Effect of interleukin 12 on in vitro HIV type 1 replication depends on clinical stage.
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 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-gamma, 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-gamma and IL-10 production. Cytokine-induced production of IL-4, IFN-gamma, 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.
Perales
M A
MA
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02155, USA.
Skolnik
P R
PR
Lieberman
J
J
D000328:Adult; D018414:CD8-Positive T-Lymphocytes; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016655:HIV Core Protein p24 / Q000032:analysis / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D016655:HIV Core Protein p24; D007376:Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12