Ultra low dose interleukin-2 therapy promotes a type I cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies

This study was undertaken to determine if prolonged daily subcutaneous administration of ultra low dose IL-2 could influence the constitutive endogenous production of a type 1 (IFN-γ) cytokine in patients with AIDS or AIDS-associated malignancies. Using a quantitative reverse transcription PCR assay, we demonstrate that daily administration of one type 1 cytokine, IL- 2, for 3 mo increases significantly the constitutive endogenous gene expression of another type 1 cytokine, IFN-γ, in vivo. The predominant source of IFN-γ appears to be IL-2-expanded natural killer cells and CD8⁺ T cells. Moreover, PBMC obtained from these patients during IL-2 therapy showed normalization of a profound deficit in IFN-γ protein production after stimulation with extracts from infectious agents in vitro. Our data suggest that prolonged exogenous administration of a type 1 cytokine in a nontoxic fashion to patients with AIDS and AIDS-associated malignancies can enhance significantly the endogenous type 1 cytokine profile in vivo. Consequently, ultra low dose IL-2 therapy has the potential to improve the immunodeficient hosts' immune response to infectious pathogens that require IFN-γ for clearance.