ANTI-INTERLEUKIN-10 ANTIBODY RESTORES BURN-INDUCED DEFECTS IN T-CELL FUNCTION

Background. Studies have shown that susceptibility to sepsis after sev ere injury correlated with reduced production of T-helper 1 (Th1) cyto kines (interleukin-[IL-2] and interferon-gamma [IFN-gamma]) and a pers istence of T-helper 2 (Th2) cytokines (IL-4 and IL-10). The mechanisms responsible for this effect are not clear. We used a T-dependent anti gen to study both the effect of burn injury on antigen-specific Th fun ctions in vivo and the effect of anti-IL-10 antibody on these function s. Methods. Male A/J mice were anesthetized and given a 25 % scald bur n or a sham burn. On day 0 all mice were immunized with 100 mu g trini trobenzene sulfonic acid (TNP) haptenated ovalbumin (TNP-OVA) in compl ete Freund's adjuvant. Mice (10 per group) were given 250 mu g monoclo nal rat antimurine IL-10 antibody (anti-IL-10 MAB) or control rat immu noglobin G (IgG) on day 0 and 100 mu g anti-IL-10 MAB or IgG on day 2. On day 10 the mice were killed to obtain serum and spleen cells. TNP- specific serum antibody isotype titers were determined by enzyme-linke d immunosorbent assay (ELISA). Splenocyte proliferation and cytokine p roduction in response to TNP-OVA or to anti-CD3 MAB were determined by tritiated thymidine incorporation and ELISA, respectively. Results, B urn injury resulted in depressed levels of the TNP-specific IgG2a anti body isotype (Th1 dependent), whereas TNP-specific IgG1 and IgE (Th2 d ependent) levels were not decreased in burn versus sham burn mice. Ant i-IL-10 MAB but not IgG restored the IgG2a response. Burn injury also resulted in reduced TNP-OVA-specific proliferation of splenocytes, whe reas anti-CD3 proliferation was equivalent in burn and sham mice. TNP- OVA-specific IL-2 and IFN-gamma production were significantly reduced by burn injury. Anti-IL-10 MAB restored TNP-OVA-specific proliferation and antigen-specific IL-2 and interferon-gamma production by splenocy tes from burn mice. Conclusions. Burn injury induces the loss of antig en-specific Th1 cell function, and IL-10 acts as a trigger to down-reg ulate Th1 activity after injury.