Interleukin-6 in islet xenograft rejection

Earlier work on primate cardiac xenotransplantation has demonstrated a corr elation between interleukin (IL)-6 levels and severity of vascular rejectio n. IL-6 was originally identified as a lymphokine inducing final maturation of B lymphocytes into antibody-secreting cells. The present study aimed to evaluate the role of IL-6 in fetal porcine islet-like cell cluster (ICC) x enograft rejection. Moreover, other authors have reported that eosinophils dominate the cellular response following discordant islet xenograft transpl antation. Here, a technique for specific detection of eosinophils was appli ed. IL-6-deficient mice and wild-type controls were implanted with fetal po rcine ICCs under the kidney capsule and killed 4-, 7-, and 10 days after tr ansplantation. Xenografts were histologically evaluated, and serum samples were analyzed for IgM and IgG antibodies against ICC membrane antigens. IL- 6-deficient mice and wild-type controls readily rejected the xenograft. On day 7 after transplantation, abundant numbers of F4/80(+) and Mac-1(+) cell s were found distributed throughout the collapsing graft accompanied by sma ll amounts of eosinophils and peripherally accumulated CD3(+) T cells (pred ominantly CD4(+)). Significantly lower serum levels of IgM and IgG antibodi es against ICC membrane antigens were observed in IL-6-deficient mice on da y 4 or 7 after transplantation when compared to wild-type controls. No sign ificant differences were seen on day 10 after transplantation. In both expe rimental groups, specific IgM and IgG antibody levels remained stable over time. In the pig-to-mouse model, IL-6 seems to be of minor importance to fe tal porcine ICC xenograft rejection. Macrophages, and not eosinophils, domi nate the cellular response associated with this process.