Interleukin-6 in islet xenograft rejection

Abstract

Earlier work on primate cardiac xenotransplantation has demonstrated a correlation between interleukin (1L)-6 levels and severity of vascular rejection. 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) xenograft rejection. Moreover, other authors have reported that eosinophils dominate the cellular response following discordant islet xenograft transplantation. Here, a technique for specific detection of eosinophils was applied. IL-6-deficient mice and wild-type controls were implanted with fetal porcine ICCs under the kidney capsule and killed 4-, 7-, and 10 days after transplantation. 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-l+ cells were found distributed throughout the collapsing graft accompanied by small amounts of eosinophils and peripherally accumulated CD3' T cells (predominantly CD4'). Significantly lower serum levels of IgM and IgG antibodies against ICC membrane antigens were observed in IL-6-deficient mice on day 4 or 7 after transplantation when compared to wild-type controls. No significant differences were seen on day 10 after transplantation. In both experimental 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 fetal porcine ICC xenograft rejection. Macrophages, and not eosinophils, dominate the cellular response associated with this process.

Advances in Innate Immunity to Overcome Immune Rejection during Xenotransplantation

“…The activation of TLR in porcine islets induced both a pro-inflammatory and procoagulant response and thereby contributed to a xenograft rejection [ 119 ]. In addition, studies have shown that immunoglobulin antibodies against islet-like cell cluster (ICC) membrane antigens are significantly reduced in the serum of IL-6-deficient mice after transplantation [ 120 ]. In addition, discordant pig-to-baboon heart xenografts show a stronger IL-6 response than congruent rhesus monkey-to-baboon xenografts [ 119 ].…”