POSTTRANSCRIPTIONAL REGULATION OF T-CELL IL-2 PRODUCTION BY HUMAN POOLED IMMUNOGLOBULIN

We evaluated the mechanism by which human pooled gamma-globulin for in travenous use (hIVIG) inhibits interleukin-2 (IL-2) production by huma n T cells. hIVIG reduced by 70-95% the amount of IL-2 in culture super natants from mitogen-stimulated peripheral blood T cells or Jurkat cel ls, This reduction was not apparent at the transcriptional level: hIVI G had no effect on the levels of IL-2 mRNA or on the accumulation of f irefly luciferase when its gene was linked to the IL-2 promoters. In c ontrast, hIVIG inhibited IL-2 protein synthesis, and the intracellular IL-2 was not restored by monensin. Our results indicate that the inhi bition of IL-2 production by hIVIG occurred posttranscriptionally, and also suggest that secretion was unaffected, and that this effect of h IVIG was specific for IL-2 (and possibly other related cytokines). The data identify a previously uncharacterized regulatory mechanism of IL -2 production and predict that this immunomodulatory effect of hIVIG m ay be significant for its therapeutic actions in immune-mediated disea ses. (C) 1997 Academic Press.