SYSTEMIC ADMINISTRATION OF CELLULAR INTERLEUKIN-10 CAN EXACERBATE CARDIAC ALLOGRAFT-REJECTION IN MICE

Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine pr oduction by T helper type 1 (Th1) cells by blocking antigen presenting cell function, This activity has suggested that IL-10 might be useful in the treatment of transplant rejection. Stimulatory effects of IL-1 0 however, have also been observed both on T and B cell differentiatio n. In this study, we examined the influence of recombinant (r) mouse ( m) IL-10 on heterotopic vascularized heart allograft survival in the B 10(H2(b))-->C3H(H2(k)) strain combination that crosses both major hist ocompatibility complex (MHC) and non-MHC-histocompatibility antigen (n on-MHC-HA) barriers, The influence of IL-10 was also examined in the B 10.BR(H2(k))-->C3H combination with disparity at only non-MHC-HA loci, Postoperative intraperitoneal administration of IL-10 (100 mu g/d, da ys 0-6) significantly accelerated heart graft rejection both in the B1 0-->C3H (mean survival time [MST] 7.8+/-0.2 days; control MST 10.6+/-0 .6 days; P<0.05) and the B10.BR-->C3H combination (MST 14.3+/-0.5 days ; control MST 77.7+/-14.4 days), Ex vivo IL-10 perfusion of donor hear ts for either 15 min or 2 hr did not affect subsequent graft survival, Immunologic monitoring of transplanted mice revealed that IL-10 treat ment (100 mu g/d, i.p., days 0-6) increased both the circulating compl ement-dependent cytotoxic (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity measured up to 3 weeks posttrans plant. These findings indicate that post transplant systemic administr ation of cIL-10 can promote vascularized allograft rejection, and that this may reflect stimulation both of B and T cell alloimmune response s.