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Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294; and Division of Surgical Research, Department of Surgery, Brown University School of Medicine, Providence, Rhode Island 02903
Macrophage (M
)
prostaglandin (PG)E2 production has been implicated in
immunosuppression and increased susceptibility to sepsis after thermal
injury. Deficient interleukin (IL)-12 production has also been
implicated in these postburn complications. The present study examined
the relationship between M
cyclooxygenase (COX)-2 activity and IL-12
production after thermal injury. C57BL/6 female mice were subjected to
a 25% total body surface area full-thickness burn. M
were isolated
7 days later, or the mice were subjected to sepsis by cecal ligation
and puncture (CLP). IL-12 production by M
from injured mice was
suppressed by >50%, whereas COX-2 expression and PGE2
production were increased twofold. The COX-2 inhibitor NS-398
suppressed PGE2 production and normalized IL-12 production
in the injury group, whereas it had no effect on IL-10 production.
Injured mice subjected to CLP had lower IL-12 plasma levels compared
with sham-treated mice subjected to CLP. NS-398 treatment prevented the
suppression in plasma IL-12 levels in the injury group. Thus elevated
M
COX-2 activity, independent of IL-10, suppresses M
IL-12
production after thermal injury and may play an important role in the
observed immunosuppression under such conditions.
prostaglandin E2; interleukin-10; immunosuppression; sepsis; burns
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