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* Research Service (151), Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220;
Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and
Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229
The cytokines IL-10 and TGF-β regulate immunity and inflammation. IL-10 is known to suppress the extent of hepatic damage caused by parasite ova during natural infection with Schistosoma mansoni, but the role of TGF-β is less clear. Cytokine blockade studies in mice revealed that anti-IL-10R mAb treatment during acute infection modestly increased cytokine production and liver damage, whereas selective anti-TGF-β mAb treatment had marginal effects. In contrast, mice administered both mAbs developed severe hepatic inflammation, with enlarged, necrotic liver granulomas, cachexia, and >80% mortality by 8 wk postinfection, despite increased numbers of CD4+CD25+Foxp3+ T regulatory cells. Blocking both IL-10 and TGF-β at the onset of egg production also significantly increased IL-4, IL-6, TNF, IFN-
, and IL-17 production and markedly increased hepatic, peritoneal, and splenic neutrophilia. In contrast, coadministration of anti-IL-10R and TGF-β mAbs had little effect upon parasite ova-induced intestinal pathology or development of alternatively activated macrophages, which are required to suppress intestinal pathology. This suggests that inflammation is controlled during acute S. mansoni infection by two distinct, organ-specific mechanisms: TGF-β and IL-10 redundantly suppress hepatic inflammation while intestinal inflammation is regulated by alternatively activated macrophages.
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1 This work was supported by the US Department of Veterans Affairs and National Institutes of Health Grants R01GM083204-01 and R01 AI052099.
2 Address correspondence and reprint requests to Dr. De’Broski R. Herbert, University of Cincinnati Department of Internal Medicine, Division of Immunology, 231 Albert Sabin Way, ML-0563, Cincinnati, OH 45267. E-mail address: herberdr{at}ucmail.uc.edu
3 Abbreviations used in this paper: Treg, T regulatory cell; IVCCA, in vivo cytokine capture assay; AST, aspartate transaminase.
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  B. Dewals, J. C. Hoving, M. Leeto, R. G. Marillier, U. Govender, A. J. Cutler, W. G.C. Horsnell, and F. Brombacher IL-4R{alpha} Responsiveness of Non-CD4 T Cells Contributes to Resistance in Schistosoma mansoni Infection in Pan-T Cell-Specific IL-4R{alpha}-Deficient Mice Am. J. Pathol., August 1, 2009; 175(2): 706 - 716. [Abstract] [Full Text] [PDF]
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