Enhancement of lymphocyte proliferation induced by interleukin-12 and anti-interleukin-10 in HIV-infected patients during highly active antiretroviral therapy

Based on the potentially important role of IL-10 and IL-12 in the pathogene sis of HIV infection, we have examined the effect of highly active antiretr oviral therapy (HAART) on the production of these two cytokines, and whethe r addition of IL-12 or anti-IL-10 in vitro could improve the proliferative response in peripheral blood mononuclear cells (PBMC) from HIV-infected pat ients during such therapy. Our findings are: (i) After initiating HAART the re were no significant changes in PHA- or MAC-PPD-stimulated IL-10 and IL-1 2 levels in PBMC supernatants in the patient group as a whole. (ii) However , while a decline in IL-10 synthesis was shown in patients with high baseli ne MAC-PPD- and PHA-stimulated IL-10 levels, IL-10 increased in patients wi th lower baseline levels. A similar pattern was seen for MAC-PPD-stimulated IL-12 levels. (iii) Exogenously added IL-12 and anti-IL-10 markedly and ad ditively improved MAC-PPD-stimulated PBMC proliferation in vitro. Thus, a l oss of cell-mediated immune response exists in HIV-infected patients also d uring apparently successful HAART and this can be significantly improved by addition of IL-12 and anti-IL-10, at least in vitro. These results suggest that further exploration of both IL-10 and IL-12 as targets for immunomodu lating therapy in HIV-infected patients in addition to HAART might be impor tant.