Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo

Blood. 1994 Oct 1;84(7):2136-43.

Abstract

We investigated the in vivo effects of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on a number of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist (IL-1Ra) in plasma in 12 patients with primary hypogammaglobulinemia. A significant and rapid increase in plasma levels of IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) was seen within 1 hour after IVIG infusion. This increase was accompanied by a more prolonged elevation in levels of both types of soluble TNF receptors (sTNFRs), which remained elevated throughout the study period (44 hours) although they reached peak levels within 1 hour. After an initial increase in the ratio between TNF alpha and sTNFRs, this ratio decreased to values significantly lower than baseline values 20 and 44 hours postinfusion with approximately 600-fold molar excess of sTNFRs to TNF alpha (trimer). Although only a modest but statistically significant increase in plasma levels of IL-1 beta was seen, IVIG infusion was followed by a marked increase in plasma levels of IL-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 several immune-mediated disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Agammaglobulinemia / therapy*
  • Aged
  • Cytokines / metabolism*
  • Female
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage*
  • Interleukin 1 Receptor Antagonist Protein
  • Male
  • Middle Aged
  • Receptors, Cytokine / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Sialoglycoproteins / metabolism*
  • Solubility
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • IL1RN protein, human
  • Immunoglobulins, Intravenous
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Cytokine
  • Receptors, Tumor Necrosis Factor
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha