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 pathogenesis of HIV infection, we have examined the effect of highly active antiretroviral therapy (HAART) on the production of these two cytokines, and whether addition of IL-12 or anti-IL-10 in vitro could improve the proliferative response in peripheral blood mononuclear cells (PBMC) from HIV-infected patients during such therapy. Our findings are: (i) After initiating HAART there were no significant changes in PHA- or MAC-PPD-stimulated IL-10 and IL-12 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 baseline MAC-PPD- and PHA-stimulated IL-10 levels, IL-10 increased in patients with 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 additively improved MAC-PPD-stimulated PBMC proliferation in vitro. Thus, a loss of cell-mediated immune response exists in HIV-infected patients also during 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 immunomodulating therapy in HIV-infected patients in addition to HAART might be important.
Stylianou
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Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department, Rikshopitalet, Oslo, Norway. eva.stylianou@klinmed.uio.no
Aukrust
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Nordøy
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Müller
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Frøland
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D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014373:Tuberculin / Q000494:pharmacology; D019562:Viral Load
D000911:Antibodies, Monoclonal; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D014373:Tuberculin; D016753:Interleukin-10; D018664:Interleukin-12