ULTRA-LOW DOSE INTERLEUKIN-2 THERAPY PROMOTES A TYPE-1 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 constitutiv e endogenous production of a type 1 (IFN-gamma) cytokine in patients w ith 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 consti tutive endogenous gene expression of another type 1 cytokine, IFN-gamm a, in vivo. The predominant source of IFN-gamma appears to be IL-2-exp anded natural killer cells and CD8(+) T cells, Moreover, PBMC obtained from these patients during IL-2 therapy showed normalization of a pro found deficit in IFN-gamma protein production after stimulation with e xtracts from infectious agents in vitro, Our data suggest that prolong ed exogenous administration of a type 1 cytokine in a nontoxic fashion to patients with AIDS and AIDS-associated malignancies can enhance si gnificantly the endogenous type 1 cytokine profile in vivo, Consequent ly, ultra low dose IL-2 therapy has the potential to improve the immun odeficient hosts' immune response to infectious pathogens that require IFN-gamma for clearance.