Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni.
Eosinophils are thought to play a major role in the immunobiology of schistosomiasis. To investigate the immunologic basis of the eosinophil response and directly assess the function of eosinophils in egg-induced pathology, mice infected with Schistosoma mansoni were injected with a monoclonal antibody produced against interleukin 5 (IL-5), a cytokine previously shown to stimulate eosinophil differentiation in vitro. This treatment suppressed the generation of eosinophil myelocyte precursors in the bone marrow and reduced to background levels the numbers of mature eosinophils in the marrow, in circulation, and within acute schistosome egg granulomas. Nevertheless, granulomas in the anti-IL-5-treated/eosinophil-depleted mice at 8 weeks of infection were only marginally smaller than those in animals injected with control monoclonal antibody, and hepatic fibrosis was comparable in the two groups. Additional parameters such as worm burden, egg output, and serum IgE levels were unaltered by the anti-IL-5 treatment. In contrast, infected animals injected with monoclonal antibody against gamma interferon (IFN-gamma) displayed circulating eosinophil levels that were elevated with respect to control mice, possibly because of an enhanced release of mature eosinophils from the marrow, and developed egg granulomas that were indistinguishable in size and cellular composition from those in control animals. Immunologic assays revealed that lymphocytes from acutely infected mice produce large quantities of IL-5 but minimal IFN-gamma when stimulated with either egg antigen or mitogen. Taken together, these results indicate that neither IL-5 nor eosinophils are essential for egg-induced pathology but suggest that lymphocytes that belong to the IL-5-producing TH2 subset predominate during acute infection and may induce granuloma formation by the production of other cytokines.
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Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Coffman
R L
RL
Hieny
S
S
Scott
P
P
Cheever
A W
AW
D000818:Animals; D000911:Antibodies, Monoclonal; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology*; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015848:Interleukin-5 / Q000276:immunology / Q000502:physiology*; D007421:Intestine, Small / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D012555:Schistosomiasis mansoni / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D013154:Spleen / Q000473:pathology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5