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Paper
December 1999

Protective Effects of Early Interleukin 10 Antagonism on Injury-Induced Immune Dysfunction

Author Affiliations

From the Department of Surgery, Section of Immunology, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.

Arch Surg. 1999;134(12):1317-1324. doi:10.1001/archsurg.134.12.1317
Abstract

Hypothesis  Interleukin 10 (IL-10) plays a central role in the development of postinjury immune suppression, and early in vivo IL-10 antagonism can be protective.

Design  Male A/J mice underwent sham or burn injury and were treated with monoclonal anti–IL-10 antibody or control antibody at 1 day or 3 days after injury. Their ability to survive polymicrobial sepsis induced by the cecum ligation and puncture (CLP) technique was then tested. The response of sham- and burn-injured mice and burn-injured mice treated with anti–IL-10 to immunization with a T-cell–dependent antigen, trinitrophenyl (TNP)–haptenated ovalbumin (TNP-OVA) was also assessed.

Main Outcome Measures  Mortality was monitored for a total of 7 days after CLP to assess the effect of anti–IL-10 therapy on the survival of burn-injured, immune-compromised mice. Serum antibody isotype formation was measured in sham- and burn-injured mice and burn-injured mice treated with anti–IL-10 to determine how IL-10 antagonism influenced helper T-cell responses in vivo. In vitro cytokine production by antigen-stimulated spleen cells was assessed to study the effect of blocking IL-10 activity at 1 day vs 3 days after burn injury.

Results  Treating mice with anti–IL-10 at 1 day after injury significantly improved CLP survival, whereas delaying treatment 3 days had no beneficial effect. The analysis of T-cell function in vivo as determined by serum antibody isotype formation indicated that anti–IL-10 treatment at 1 day or 3 days after injury increased T helper cell 1–type antibody formation to sham injury levels by day 10. Moreover, these treatments restored the injury-induced reduction of antigen-stimulated IL-2, interferon γ, and IL-10 production.

Conclusions  Interleukin 10 plays an early role in the development of burn injury–induced immune suppression. Its in vivo inhibition at 1 day after injury may be a useful approach toward preventing the development of injury-induced immune dysfunction and may do so by restoring T-cell function and cytokine production.

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