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Release of cytokines, soluble cytokine receptors, and interleukin-1
receptor antagonist after intravenous immunoglobulin administration in vivo
P Aukrust, SS Froland, NB Liabakk, F Muller, I Nordoy, C Haug and T Espevik
Medical Department A, Kaptein W. Wilhelmsen og frues Institute of
Bacteriology, University of Oslo, Norway.
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.
Volume 84,
Issue 7,
pp. 2136-2143,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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