Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Print ISSN: 0006-4971 (Print) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York] : Elsevier
      Original Publication: New York, Grune & Stratton [etc.]
    • Subject Terms:
      Hypotension/*etiology ; Immunoglobulin G/*toxicity ; Immunoglobulins, Intravenous/*toxicity ; Phospholipases A/*therapeutic use ; Platelet Activating Factor/*metabolism ; Receptors, IgG/*physiology; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Dimerization ; Drug Stability ; Female ; Humans ; Hypotension/prevention & control ; Immunoglobulin G/pharmacology ; Macrophages/drug effects ; Macrophages/metabolism ; Neutrophils/drug effects ; Neutrophils/metabolism ; Phospholipases A/genetics ; Phospholipases A/pharmacology ; Rats ; Rats, Wistar ; Receptors, IgG/antagonists & inhibitors ; Recombinant Fusion Proteins/pharmacology ; Recombinant Fusion Proteins/therapeutic use
    • Abstract:
      Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by platelet-activating factor (PAF) produced by macrophages. In this study, we compared the vasoactive effects of 16 intravenous immunoglobulin (IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the IgG dimer content of the preparations. Pretreatment of the rats with recombinant PAF acetylhydrolase completely prevented the hypotensive reaction on IVIG infusion, and administration after the onset of hypotension resulted in normalization of the blood pressure. We also observed PAF production on in vitro incubation of human neutrophils with IVIG, which could be blocked by anti-Fcgamma receptor antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of IVIG in patients may be caused by macrophage and neutrophil activation through interaction of IgG dimers with Fcgamma receptors. Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions. (Blood. 2000;95:1856-1861)
    • Accession Number:
      0 (Immunoglobulin G)
      0 (Immunoglobulins, Intravenous)
      0 (Platelet Activating Factor)
      0 (Receptors, IgG)
      0 (Recombinant Fusion Proteins)
      EC 3.1.1.32 (Phospholipases A)
      EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase)
    • Publication Date:
      Date Created: 20000226 Date Completed: 20000329 Latest Revision: 20210216
    • Publication Date:
      20221213
    • Accession Number:
      10688848