부산대학교 도서관

OBJECTIVE:: To evaluate the impact of age on the proliferative response, cytokine profile and viral kinetics in AIDS patients treated successfully with antiretroviral drugs. METHODS:: Peripheral blood mononuclear cells (PBMC), CD4 cell-depleted PBMC or CD4 T cells from young adult and aged HIV-1-infected patients were activated in vitro with anti-CD3 with or without interleukin (IL)-2. Lymphoproliferation and cytokines were measured after 3 days and in-vitro HIV-1 replication after 7 days. RESULTS:: Both lymphoproliferation and cytokine [IL-1β, tumour necrosis factor α (TNF-α) and interferon γ (IFN-γ)] secretion were higher in younger than in older AIDS patients. In cultures of cells derived from aged patients and activated by anti-CD3, IFN-γ production was severely damage and IL-10 production was much higher. Although IL-2 addition to activated PBMC elevated IFN-γ secretion, IL-10 production remained elevated in the aged group. The depletion of CD4 T lymphocytes from these cultures dramatically reduced released IL-10 in the older group but did not alter significantly IFN-γ production. Interestingly, higher IL-10 levels produced by CD4 T cells were related to lower in-vitro HIV-1 replication, and the blockade of this cytokine by anti-IL-10 monoclonal antibody enhanced virus replication. This effect may be correlated with elevated TNF-α secretion. Finally, impaired IFN-γ secretion detected in activated CD4 T cells obtained from aged patients was not directly correlated with high IL-10 production. CONCLUSIONS:: Elevated IL-10 production by aged AIDS patients contributed considerably to control of HIV replication and to inhibition of TNF-α secretion but not to the reduced IFN-γ production.