Sg. Qian et al., SYSTEMIC ADMINISTRATION OF CELLULAR INTERLEUKIN-10 CAN EXACERBATE CARDIAC ALLOGRAFT-REJECTION IN MICE, Transplantation, 62(12), 1996, pp. 1709-1714
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.