Immunoregulatory role of the Type 1 cytokines in the immune responses of patients with chronic renal failure (CRF) and a murine model of graft-versus-host disease (GVHD)

Abstract

The aim of the present study was to elucidate the role of regulatory type 1 cytokines, particularly IL-12 and IFN-[gamma] in the mechanisms by which the immune responses are suppressed or augmented. The hypothesis was that in patients with CRF, impaired immunity is caused by a defective T cell activation due to the lack of Th1-like regulatory cytokines, i.e. IL-12 and IFN-[gamma]. We further hypothesized that in bone marrow recipients, GVHD is developed due to the activation of T cells and NK cells in parallel with the overexpression of these cytokines. Specifically, in addition to the effects of the presence of IL-12 on in vitro cellular responses of patients with CRF, we examined serum TNF-[alpha] levels of IL-12 KO and IFN-[gamma] KO mice after systemic LPS treatments. We also aimed to investigate the differences between the degree of intestinal damage occurring during the GVH reaction and its relationship with the level of LPS-induced serum TNF-[alpha]. (Abstract shortened by UMI.)