BACKGROUND: Systemic inflammation has been linked to a failure to normalize CD4(+) T-cell numbers in treated human immunodeficiency virus (HIV) infection. Although inflammatory cytokines such as interleukin 6 (IL-6) are predictors of disease progression in treated HIV infection, it is not clear how or whether inflammatory mediators contribute to immune restoration failure.METHODS: We examined the in vitro effects of IL-6 and interleukin 1â (IL-1â) on peripheral blood T-cell cycling and CD127 surface expression.RESULTS: The proinflammatory cytokine IL-1â induces cell cycling and turnover of memory CD4(+) T cells, and IL-6 can induce low-level cycling of naive T cells. Both IL-1â and IL-6 can decrease T-cell surface expression and RNA levels of CD127, the interleukin 7 receptor á chain (IL-7Rá). Preexposure of healthy peripheral blood mononuclear cells (PBMCs) to IL-6 or IL-1â attenuates IL-7-induced Stat5 phosphorylation and induction of the prosurvival factor Bcl-2 and the gut homing integrin á4â7. We found elevated expression of IL-1â in the lymphoid tissues of patients with HIV infection that did not normalize with antiretroviral therapy.CONCLUSIONS: Induction of CD4(+) T-cell turnover and diminished T-cell responsiveness to IL-7 by IL-1â and IL-6 exposure may contribute to the lack of CD4(+) T-cell reconstitution in treated HIV-infected subjects.
Antiretroviral Therapy, Highly Active CD4-Positive T-Lymphocytes