Differential dose effects of recombinant IL-25 on the development of dextran sulfate sodium-induced colitis.
OBJECTIVE
We evaluated different dose effects of rIL-25 on acute ulcerative colitis.


METHODS
Mice were fed 2.5% dextran sulfate sodium (DSS) for 5 days while infused i.p. with repeated doses of rIL-25 (0.2, 0.4 and 0.8 microg) in PBS or PBS only after every 24 h at the same time as the start of the DSS exposure. Clinical, macroscopical and microscopical assessment of colitis severity with survival study was performed. Colonic IL-25 expression and production of IFN-gamma, IL-10 and IL-4 was also analyzed.


RESULTS
At a dose of 0.2 microg, colitis was aggravated with high mortality, better improvements were observed at a dose of 0.4 microg, and colitis-induced diarrhea was reversed at a dose of 0.8 microg. The expression of IL-25 was found to decrease in severe colitis. Moreover, IL-25 inhibited production of mucosal IFN-gamma, induced increase in IL-10 but not IL-4.


CONCLUSIONS
Improvements in DSS-induced colitis in response to IL-25 suggest IL-25's protective role by mechanisms including inhibition of IFN-gamma with enhancement of anti-inflammatory release.
Mchenga
S S Salum
SS
Department of Immunology, College of Basic Medical Science, China Medical University, 92, North second road, Heping District, Shenyang 110001, China. salummchenga@yahoo.com
Wang
D
D
Janneh
F M
FM
Feng
Y
Y
Zhang
P
P
Li
Z
Z
Lu
C
C
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*
D007378:Interleukins; C442281:Mydgf protein, mouse; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016264:Dextran Sulfate