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Departments of
*
Internal Medicine and
Pathology, University of Iowa College of Medicine, Iowa City, IA 52242
IL-10 is a potent anti-inflammatory and immune regulatory
cytokine. IL-10-/- mice produce exaggerated amounts of
inflammatory cytokines when stimulated with LPS, indicating that
endogenous IL-10 is a central regulator of inflammatory cytokine
production in vivo. PGs are lipid mediators that are also produced in
large amounts during the inflammatory response. To study the role of
IL-10 in the regulation of PG production during the acute inflammatory
response, we evaluated LPS-induced cyclooxygenase (COX) expression and
PG production in wild-type (wt) and IL-10-/- mice.
LPS-induced PGE2 production from IL-10-/-
spleen cells was 5.6-fold greater than that from wt spleen cells. LPS
stimulation resulted in the induction of COX-2 mRNA and protein in both
wt and IL-10-/- spleen cells; however, the magnitude of
increase in COX-2 mRNA was 5.5-fold greater in IL-10-/-
mice as compared with wt mice. COX-1 protein levels were not affected
by LPS stimulation in either wt or IL-10-/- mice.
Neutralization of IFN-
, TNF-
, or IL-12 markedly decreased the
induction of COX-2 in IL-10-/- spleen cells, suggesting
that increased inflammatory cytokine production mediates much of the
COX-2 induction in IL-10-/- mice. Treatment of
IL-10-/- mice with low doses of LPS resulted in a marked
induction of COX-2 mRNA in the spleen, whereas wt mice had minimal
expression of COX-2 mRNA. These findings indicate that, in addition to
IL-10’s central role in the regulation of inflammatory cytokines,
endogenous IL-10 is an important regulator of PG production in the
response to LPS.
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