IL-10 is crucial for the transition from acute to chronic disease state during infection of mice with Schistosoma mansoni.
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.
Sadler
Clare H
CH
Department of Biology, University of York, York, GB.
Rutitzky
Laura I
LI
Stadecker
Miguel J
MJ
Wilson
R Alan
RA
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
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D016753:Interleukin-10