Induction of chronic colitis in IL-10 deficient mice requires IL-4.
Th 1 cells activated by IL-12 and secreting IFN-gamma have been described as the main mediators for onset and maintenance of chronic colitis in IL-10 deficient mice. It was therefore surprising that mice deficient for IL-4 in addition to IL-10 showed intestinal pathology very rarely, whereas IL-10 KO mice developed rectal prolapse in most cases. To investigate the underlying mechanisms, we studied changes of ongoing inflammatory processes in mice deficient for IL-4, IL-10 or both cytokines. Levels of IFN-gamma, IL-12p40 and MHCII mRNA were elevated to a much higher degree in colonic tissue of IL-10 KO compared to IL-4/10 KO at the onset of colitis. Furthermore, the influx of eosinophils, a marker for Th2 responses, was investigated. Only IL-10 deficient mice displayed a significant increase of eosinophils in the lamina propria of the colon and rectum. In contrast, IL-4/10 deficient mice had eosinophil levels comparable to wildtype controls and IL-4 KO. Together these results indicate an important role of IL-4 for the onset of colitis in IL-10 KO mice by promoting a Th1 response and induction of a deleterious Th2 effector response.
Specht
Sabine
S
Institute for Medical Parasitology, Friedrich Wilhelm University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany. specht@parasit.meb.uni-bonn.de
Arriens
Sandra
S
Hoerauf
Achim
A
D000818:Animals; D018946:Chemokine CCL5 / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D005243:Feces / Q000737:chemistry; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000032:analysis; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D018946:Chemokine CCL5; D007074:Immunoglobulin G; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4