Expression of interleukin-10 in vitro and in vivo.

Abstract

Classification of cytokines into T helper type 1 (Th1) and T helper type 2 (Th2) has helped in the elucidation of the mechanisms of resistance or susceptibility to infections. HIV infection causes CD4$\sp+$ T cell dysfunction and depletion by indirect mechanisms; for example: inhibition of immunoregulatory cytokines. Interleukin (IL-10), the subject of this study, is secreted mostly by CD4$\sp+$ human Th2-like, but also by Th0,Th1-like, and by a proportion of CD8$\sp+$ T cell clones. HIV sero-positive patients exhibit depressed cell mediated immune responses, B cell hyperplasia, and hypergammaglobulinemia which may result from downregulation of Th1 and upregulation of Th2 class responses respectively. In this study, the expression of interferon$\gamma$ (IFN$\gamma$) and IL-10 which mediate Th1 and Th2 responses respectively, in unstimulated peripheral blood lymphocytes (PBLs) from HIV$\sp+$ patients were investigated. IL-10 expression as observed by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis was significantly upregulated in patients with less than 400 CD4$\sp+$ T cells in comparison with HIV$\sp+$ patients with more than 400 CD4$\sp+$ T cells and normal controls. A semi-quantitative RT-PCR analysis of unstimulated PBLs further demonstrated IL-10 upregulation was inversely associated with IFN$\gamma$ downregulation in the same individuals. Similar results were observed as determined by measuring IL-10 and IFN$\gamma$ production in the supernatants of unstimulated PBLs by employing enzyme immunoassay techniques. These results suggest that HIV infected individuals express predominately Th2 type cytokines in their PBLs.