RT Journal
A1 Lyons A, Goebel A, Mannick JA, Lederer JA
T1 PRotective effects of early interleukin 10 antagonism on injury-induced immune dysfunction
JF Archives of Surgery
JO Archives of Surgery
YR 1999
FD December 1
VO 134
IS 12
SP 1317
OP 1324
DO 10.1001/archsurg.134.12.1317
UL http://dx.doi.org/10.1001/archsurg.134.12.1317
AB 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.