RELEASE OF CYTOKINES, SOLUBLE CYTOKINE RECEPTORS, AND INTERLEUKIN-1 RECEPTOR ANTAGONIST AFTER INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION IN-VIVO

We investigated the in vivo effects of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on a number of cytokines, solubl e cytokine receptors, and interleukin-1 receptor antagonist (IL-1Ra) i n plasma in 12 patients with primary hypogammaglobulinemia. A signific ant and rapid increase in plasma levels of IL-6, IL-8, and tumor necro sis factor alpha (TNF alpha) was seen within 1 hour after IVIG infusio n. This increase was accompanied by a more prolonged elevation in leve ls of both types of soluble TNF receptors (sTNFRs), which remained ele vated throughout the study period (44 hours) although they reached pea k levels within 1 hour. After an initial increase in the ratio between TNF alpha and sTNFRs, this ratio decreased to values significantly lo wer than baseline values 20 and 44 hours postinfusion with approximate to 600-fold molar excess of sTNFRs to TNF alpha (trimer). Although on ly a modest but statistically significant increase in plasma levels of IL-1 beta was seen, IVIG infusion was followed by a marked increase i n plasma levels of 1L-1Ra with 1,000-fold molar excess of IL-1Ra to IL -1 beta in some patients. The demonstrated effects of IVIG infusion on the cytokine network, particularly the induction of IL-1Ra and sTNFRs release, might be important for the therapeutic effects of IVIG in se veral immune-mediated disorders. (C) 1994 by The American Society of H ematology.