IgG for intravenous use, autologous serum and plasma induce comparable interleukin-1 receptor antagonist liberation from human mononuclear cells: An in vitro phenomenon depending upon plastic adherence

Immunoglobulin G (IgG) for intravenous use (IVIg) selectively stimulates production of interleukin-1 receptor antagonist protein (IL-1ra) by mononuclear cells in vitro and has been proposed to stimulate IL-1ra production in vivo as part of the therapeutic effect. We tested if IVIg differed from human IgG-containing media (i.e., autologous serum (HS) and plasma (HP)) in stimulating IL-1ra release by MNC in vitro and whether IVIg induced a delayed increase in serum levels of IL-1ra. IVIg, 0.01-0.5 mg/ml, increased the IL-1ra liberation from MNC 10-15 times over that of untreated controls. HP and HS (5% v/v) had comparable effects. However, the stimulated IL-1ra liberation was reduced to less than twice the background liberation when fetal calf serum (FCS)-precoated tubes were used. Three days of high-dose IgG infusion had no significant effect on the serum levels of IL-1ra. It is concluded that therapeutic effects of IVIg cannot be ascribed to significant stimulation of IL-1ra production in vivo, as previously suggested, and that the observed stimulation of IL-1ra production in vitro is an epiphenomenon strictly dependent upon adherence of human serum and plasma constituents.