• Danila Leontyev, Anton Neschadim, and Donald R Branch.
• Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Advanced Diagnostics, Infection and Immunity Group, Toronto General Research Institute, Toronto, Ontario, Canada.
• Transfusion. 2014 Nov 1; 54 (11): 2871-9.

BackgroundMouse models of human immune thrombocytopenia (ITP) have been used for years to investigate the mechanism of intravenous immunoglobulin (IVIG) to ameliorate ITP; however, how closely these experimental mouse models mirror the human autoimmune inflammatory disease is unclear. The aim of this study was to assess the cytokine profiles in experimental ITP with and without IVIG treatment.Study Design And MethodsWe examined the production of 23 cytokines that included pro- and anti-inflammatory cytokines, in two different mouse strain models of ITP, BALB/c and C57BL/6J, with and without IVIG treatment.ResultsIn contrast to human ITP, in mouse models of ITP generated by passive transfer of an alloantibody we find no evidence of inflammatory disease even when ITP is robust, suggesting that while these models capture the innate response phase of the disease, they may not be capturing the adaptive mechanisms of autoimmune initiation of the disorder. Regardless of the mouse strain examined, interleukin (IL)-1α, -2, -6, -17, and -23; granulocyte-macrophage-colony-stimulating factor (GM-CSF); monocyte chemoattractant protein (MCP)-1; macrophage inflammatory protein (MIP)-1β; RANTES; tumor necrosis factor (TNF)-α; and interferon-γ remain at negligible levels after ITP induction. IVIG treatment in the absence of ITP induced significant levels of IL-4, -10, -11, -17, and -23; GM-CSF; MCP-1; and TNF-α in BALB/c mice, but only IL-11 was elevated in C57BL/6J mice. In response to IVIG treatment of ITP, both strains produced IL-4, -10, -11, and -23; GM-CSF; MCP-1; MIP-1β; and TNF-α; however, only BALB/c exhibited increased MCP-3 and RANTES. IL-11 levels were the highest of any cytokine after IVIG administration, given either alone or as treatment of ITP.ConclusionsWe conclude that mouse models for human ITP do not capture the full range of autoimmune inflammatory mechanisms of this disease. Furthermore, cytokine profiles differ in response to IVIG depending on the mouse strain used.© 2014 AABB.

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