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In vitro production of interleukin‐1 receptor antagonist in IgG‐ mediated red cell incompatibility
Author(s) -
Davenport R.D.,
Burdick M.D.,
Strieter R.M.,
Kunkel S.L.
Publication year - 1994
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.1994.34494233576.x
Subject(s) - peripheral blood mononuclear cell , hemolysis , receptor antagonist , immune system , interleukin 2 , immunology , biology , receptor , interleukin 1 receptor antagonist , cytokine , interleukin , microbiology and biotechnology , in vitro , chemistry , antagonist , biochemistry
Background : Recently, proinflammatory cytokines including interleukin 1 (IL‐1) have been implicated in the pathophysiology of immune‐mediated hemolysis. Little is known, however, about the mechanisms by which inflammatory events in these reactions may be downregulated. IL‐1 receptor antagonist (IL‐1ra) inhibits the actions of IL‐1 by competition for cellular receptors, and thus it may regulate the biologic actions of IL‐1 during immune‐mediated hemolysis. The production of IL‐1ra by peripheral blood mononuclear cells (PBMNCs) in response to IgG‐coated red cells in vitro was investigated. Study Design and Methods : Fresh PBMNCs were obtained by density gradient separation of heparinized whole blood. PBMNCs were cultured in the presence of anti‐D‐coated, Rh‐positive red cells or uncoated Rh‐ negative red cells under nonadherent conditions. IL‐1ra concentrations in the culture media were measured by enzyme‐linked immunosorbent assay. IL ‐1 ra and IL ‐1β gene expression was assessed by Northern blot analysis of PBMNC mRNA. Results : IL‐1ra production was evident 4 hours after stimulation with IgG‐coated red cells and increased progressively over 24 hours. Gene expression of IL‐1ra was first detected at 2 hours, lagging behind that of IL‐1β. IL‐1ra gene expression was not inhibited by neutralizing polyclonal antibodies to IL‐1. Immunocytochemical staining to determine the cellular source localized IL‐1ra production to monocytes engaged in erythrophagocytosis. IL‐1ra production was inhibited by dexamethasone (10 −7 M ). Conclusion : These results suggest that IL‐1ra production may partly account for the variable pathophysiologic events seen in IgG‐ mediated autoimmune hemolysis and hemolytic transfusion reactions. Steroid treatment may also downregulate anti‐inflammatory cytokine production in immune hemolysis.