title: Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions.
abstract: Cytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor-alpha (TNF-alpha), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon-gamma (IFN-gamma) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10023, USA.
authors.forename: Eldad A
authors.initials: EA
authors.lastname: Hod
authors.forename: Chantel M
authors.initials: CM
authors.lastname: Cadwell
authors.forename: Justine S
authors.initials: JS
authors.lastname: Liepkalns
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
authors.forename: Set A
authors.initials: SA
authors.lastname: Sokol
authors.forename: David A
authors.initials: DA
authors.lastname: Schirmer
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jhang
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
mesh_terms: D000818:Animals; D001787:Blood Group Incompatibility; D016207:Cytokines / Q000096:biosynthesis*; D006021:Glycophorins; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D007249:Inflammation; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D065227:Transfusion Reaction
chemical_list: D016207:Cytokines; D006021:Glycophorins; D007074:Immunoglobulin G