Altered cytokine expression in mesenteric lymph nodes in a rat strain (Matsumoto Eosinophilic Shinshu) that spontaneously develops hypereosinophilia

Summary The Matsumoto Eosinophilic Shinshu (MES) rat is an inbred mutant strain that spontaneously develops systemic hypereosinophilia with eosinophilic inflammatory lesions similar to those associated with hypereosinophilic syndrome in humans and other mammals. To elucidate the pathogenic mechanisms that underlie these features of MES rats, we examined the pattern of cytokine gene expression in mesenteric lymph nodes (MLNs), the thymus, and peripheral blood mononuclear cells as well as the blood clinicopathology and MLN lymphocytic subsets of these animals. MES rats exhibited both leucocytosis, attributable in large part to hypereosinophilia and neutrophilia, and immunoglobulin M (IgM) and IgA gammaglobulinaemia, with increased titres of IgM autoantibodies to nuclear antigens. Reverse transcription and polymerase chain reaction analysis revealed that the amounts of interleukin (IL)-5, IL-4, eotaxin, and interferon-γ mRNAs were increased in the MLN lymphocytes of MES rats compared with the corresponding values for Sprague-Dawley rats. Intraperitoneal administration of a monoclonal antibody specific for IL-5 resulted in an immediate suppression of hypereosinophilia and a delayed suppression of neutrophilia in MES rats. Flow cytometry revealed an increased percentage of CD3+ CD4– CD8– T lymphocytes in MLNs of MES rats. Our results suggest that the hypereosinophilia of MES rats results from an increased production of IL-5, and that the eosinophilic inflammatory lesions of these animals, which are largely restricted to the gut, may be related both to cytokine overexpression in MLNs and to T helper 1 and 2 immunological responses.