title: IL-10 is crucial for the transition from acute to chronic disease state during infection of mice with Schistosoma mansoni.
abstract: After infection of mice with Schistosoma mansoni, deposition of eggs in the walls of the intestine and liver provokes an intense (acute) T cell response that peaks at week 8 and, thereafter, down-modulates as the disease becomes chronic. Egg antigen-stimulated proliferation of mesenteric lymph node and spleen cells in vitro was intense at week 8 in both IL-10(-/-) and wild-type (WT) mice, while proliferative responses were markedly reduced at week 15 in WT mice, but undiminished in IL-10(-/-) animals. Moreover, in the absence of IL-10 production, levels of both IFN-gamma and IL-4 remained elevated at week 15. Granulomas around eggs embolized in the livers of WT mice were significantly smaller at week 15 than week 8, whereas those in IL-10(-/) animals were larger at week 8, showed no reduction in size at week 15, and were less sharply demarcated by peripheral collagen. There was also a greater leukocytic infiltration and necrosis of the hepatic parenchyma. These data suggest that in mice IL-10 regulates not only the intensity of hepatic inflammation, but also granuloma organization and cohesiveness. It is a crucial agent in the down-modulation of immune responses and immunopathology that defines the transition from acute to chronic disease.
authors.affiliation: Department of Biology, University of York, York, GB.
authors.forename: Clare H
authors.initials: CH
authors.lastname: Sadler
authors.forename: Laura I
authors.initials: LI
authors.lastname: Rutitzky
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Stadecker
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
mesh_terms: D000208:Acute Disease; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006099:Granuloma / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D016753:Interleukin-10