GM‐CSF and IL‐4 are not involved in IVIG‐mediated amelioration of ITP in mice: a role for IL‐11 cannot be ruled out

Previously, we have reported that interleukin (IL)‐4, granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and IL‐11, but not IL‐33, are up‐regulated in two strains of mice with immune thrombocytopenia (ITP) that are responsive to intravenous immunoglobulin (IVIg) treatment. Previously, IL‐4 was ruled out in the mechanism of IVIg; however, other publications have suggested this cytokine as a major player in the mechanism of IVIg action. Thus, we sought to further investigate a role for IL‐4 and, in addition, GM‐CSF and IL‐11 in the mechanism of action of IVIg using a murine model of ITP. A passive platelet antibody model was used to generate ITP in IL‐4 receptor knock‐out (IL‐4R–/–), IL‐11 receptor knock‐out (IL‐11Rα–/–) and GM‐CSF knock‐out (Csf2–/–) mice. We also used a neutralizing antibody to IL‐11 and recombinant human IL‐11 (rhIL‐11) in addition to depleting basophils in vivo to study the effect of IVIg to ameliorate ITP. Our results showed that basophils, IL‐4 and GM‐CSF were unimportant in both ITP induction and its amelioration by IVIg. The role of IL‐11 in these processes was less clear. Even though IL‐11Rα–/– mice with ITP responded to IVIg similarly to wild‐type (WT) mice, treatment of ITP WT mice with rhIL‐11 instead of IVIg showed an increase in platelet numbers and WT mice administered anti‐IL‐11 showed a significant reduction in the ability of IVIg to ameliorate the ITP. Our findings indicate that neither IL‐4, basophils or GM‐CSF have roles in IVIg amelioration of ITP; however, a role for IL‐11 requires further study.