INTERLEUKIN-12 ADMINISTERED IN-VIVO DECREASES HUMAN NK CELL CYTOTOXICITY AND ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY TO HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CELLS

Persons infected with human immunodeficiency virus (HIV) have cellular cytotoxicity defects, Interleukin (IL)-12 is a potent stimulator of c ytotoxicity. Fifteen HIV-infected patients were studied in a phase 1, single-dose escalation trial of human recombinant IL-12. One day after subjects received an IL-12 dose of 300 or 1000 ng/kg, they had a redu ction in absolute lymphocyte count and peripheral blood mononuclear ce ll recovery, In evaluable patients 24 h after IL-12 administration, th ere was a 31% reduction overall in NK cell cytotoxicity (NKC) to HIV-i nfected cells at all doses and a 52% reduction in antibody-dependent c ellular cytotoxicity (ADCC) at doses of 300 and 1000 ng/kg, In vitro i ncubation of patients' cells with IL-12 (before IL-12 administration) for 24 h increased NKC but had no effect on ADCC. The paradoxic acute reduction in cell number and cytotoxicity in vivo may be due to NK cel l trafficking or regulatory cytokine mechanisms not apparent in vitro.