Systemic administration of cellular interleukin-10 can exacerbate cardiac allograft rejection in mice.
Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine production 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-10 however, have also been observed both on T and B cell differentiation. In this study, we examined the influence of recombinant (r) mouse (m) IL-10 on heterotopic vascularized heart allograft survival in the B10(H2b)-->C3H(H2k) strain combination that crosses both major histocompatibility complex (MHC) and non-MHC-histocompatibility antigen (non-MHC-HA) barriers. The influence of IL-10 was also examined in the B10.BR (H2k)--> C3H combination with disparity at only non-MHC-HA loci. Postoperative intraperitoneal administration of IL-10 (100 microg/d, days 0-6) significantly accelerated heart graft rejection both in the B10-->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 hearts for either 15 min or 2 hr did not affect subsequent graft survival. Immunologic monitoring of transplanted mice revealed that IL-10 treatment (100 microg/d, i.p., days 0-6) increased both the circulating complement-dependent cytotoxic (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity measured up to 3 weeks posttransplant. These findings indicate that post transplant systemic administration of cIL-10 can promote vascularized allograft rejection, and that this may reflect stimulation both of B and T cell alloimmune responses.
Qian
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Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
Li
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W
Li
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Fu
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F
Lu
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Fung
J J
JJ
Thomson
A W
AW
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D016753:Interleukin-10 / Q000008:administration & dosage*; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications; D011994:Recombinant Proteins / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology
D011994:Recombinant Proteins; D016753:Interleukin-10