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 stimulat es 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 IVI g differed from human IgG-containing media (i.e., autologous serum (HS ) and plasma (HP)) in stimulating IL-1ra release by MNC in vitro and w hether 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 ef fects. However, the stimulated IL-1ra liberation was reduced to less t han twice the background liberation when fetal calf serum (FCS)-precoa ted tubes were used. Three days of high-dose IgG infusion had no signi ficant effect on the serum levels of IL-1ra. It is concluded that ther apeutic effects of IVIg cannot be ascribed to significant stimulation of IL-1ra production in vivo, as previously suggested, and that the ob served stimulation of IL-1ra production in vitro is an epiphenomenon s trictly dependent upon adherence of human serum and plasma constituent s.