Jf. Modiano et al., POSTTRANSCRIPTIONAL REGULATION OF T-CELL IL-2 PRODUCTION BY HUMAN POOLED IMMUNOGLOBULIN, Clinical immunology and immunopathology, 83(1), 1997, pp. 77-85
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.