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*
Department of Molecular Biology, DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, CA 94304;
Department of Immunology, University of Cape Town, Cape Town, South Africa; and
Schering-Plough Research Institute, Lafayette, NJ 07848
IL-4 is associated with Th2-type immune responses and can either
inhibit or, in some cases, promote Th1-type responses. We tested the
effect of IL-4 treatment on the development of inflammation in the
CD4+CD45RBhigh T cell transfer model of
colitis, which has been characterized as a Th1-dependent disease. IL-4
treatment significantly accelerated the development of colitis in
immunodeficient recipients (recombinase-activating gene-2
(Rag2)-/-) of CD4+CD45RBhigh T
cells. Quantitative analysis of mRNA expression in the colons of
IL-4-treated mice showed an up-regulation of both Th1- and
Th2-associated molecules, including IFN-
, IP-10, MIG, CXCR3,
chemokine receptor-8, and IL-4. However, cotreatment with either IL-10
or anti-IL-12 mAb effectively blocked the development of colitis in
the presence of exogenous IL-4. These data indicate that IL-4 treatment
exacerbates a Th1-mediated disease rather than induces Th2-mediated
inflammation. As other cell types besides T cells express the receptor
for IL-4, the proinflammatory effects of IL-4 on host cells in
Rag2-/- recipients were assessed. IL-4 treatment was able
to moderately exacerbate colitis in Rag2-/- mice that
were reconstituted with IL-4R
-deficient (IL-4R-/-)
CD4+CD45RBhigh T cells, suggesting that the
IL-4 has proinflammatory effects on both non-T and T cells in this
model. IL-4 did not cause colitis in Rag2-/- mice in the
absence of T cells, but did induce an increase in MHC class II
expression in the lamina propria of the colon, which was blocked by
cotreatment with IL-10. Together these results indicate that IL-4 can
indirectly promote Th1-type inflammation in the
CD4+CD45RBhigh T cell transfer model of
colitis.
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