Differential Production of Interleukin 10 during Human Immunodeficiency Virus Infection

Abstract

Interleukin 10, a product of T and B cells and monocytes, displays many Th2-like properties through inhibition of Thl cell functions. Interleukin 10 is thought to play a major role in the immune dysfunction seen in HIV-infected individuals. In this study, we evaluated in detail the production of IL-10 during HIV infection. Although the constitutive production of IL-10 did not differ in PBMCs from healthy donors and HIV-infected individuals, IL-10 was differentially produced in response to polyclonal activators. The overall plasma IL-10 levels were similar in 32 controls and 67 patients at different stages of the disease and receiving different antiretroviral drugs. However, patients with low CD4 T cell count (<200/mm³) secreted approximately three-fold more IL-10 than did patients with high CD4 T cell count (>500/mm³). Competitive/quantitative PCR revealed similar levels of mRNA expression in PBMCs from controls and HIV-infected individuals. In vitro HIV infection rapidly and transiently induced IL-10 production in PBMCs and monocytes, and the low level of endogenously secreted IL-10 failed to inhibit HIV replication in acutely infected monocytes. On the other hand, HIV infection of selected CD4⁺ T cell clones generated in a Thl- or Th2-like environment, differentially upregulated IL-10 production, with significantly higher production by Th2 clones. Together, our data indicate that IL-10 production is more complex than previously thought, and may depend on several factors such as producer cells, nature of the stimuli, as well as viral isolates.