Downregulation of Interferon

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. In evaluating the role of IFN as therapeutic agents in AIDS, we investigated the expression of IFNa and 'y receptors on peripheral blood mononuclear cells (PBM) from patients with AIDS, ARC, and heterosexual control subjects using radioiodinated IFNa2 and IFN-y. The binding characteristics of the 1"I-IFNa and y to PBM were analyzed to determine receptor numbers and dissociation constants. PBM from controls expressed 498±247 IFNa receptor sites/cell (n = 17). However, eight patients with ARC and seven patients with AIDS had a mean number of IFNa receptor/cell of 286±235 (P < 0.05) and 92±88 (P < 0.001), respectively. This was consistent with elevated levels of serum acid-labile IFNa and cellular 2-5A synthetase activity in patients. Treatment ofPBM from the AIDS patients with exogenous IFNa in vitro resulted in minimal 2-5A synthetase induction in comparison to controls. In contrast, the expression of IFN'y receptors in ARC (a = 5) and AIDS (a = 4) patients remained normal. Thus the decrease in IFNa receptor expression and consequent hyporesponsiveness to IFNa raises the question of the usefulness of IFNa therapy in end-stage AIDS. The normal expression of IFN'y receptors in AIDS patients suggests that IFNy may prove useful in attempts to provide immune reconstitution.