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, 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.
Aukrust
P
P
Medical Department A, Kaptein W. Wilhelmsen og frues Institute of Bacteriology, University of Oslo, Norway.
Frøland
S S
SS
Liabakk
N B
NB
Müller
F
F
Nordøy
I
I
Haug
C
C
Espevik
T
T
D000328:Adult; D000361:Agammaglobulinemia / Q000628:therapy*; D000368:Aged; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; C507763:IL1RN protein, human; D016756:Immunoglobulins, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D018121:Receptors, Cytokine; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha