Induction of syngeneic graft-versus-host disease in LPS hyporesponsive C3H/HeJ mice

Syngeneic GVHD (SGVHD) develops following syngeneic bone marrow transplanta tion and treatment with cyclosporine A. Previous studies have demonstrated a role for IL-12, IFN-gamma, and TNF-a in the development of murine SGVHD. Macrophages can he activated to secrete IL-12 and TNF-alpha via a T-cell-de pendent or T-cell-independent pathway (LPS or bacterial products). Studies were designed to determine if LPS participated in the development of SGVHD in C3H/HeN (LPS-responsive) and C3H/HeJ (LPS-hyporesponsive) mice. C3H/HeJ and C3H/HeN mice had similar levels of disease induction and pathology. Fol lowing induction of SGVHD, treatment of C3H/HeN, but not C3H/HeJ, mice with a sublethal dose of LPS resulted in mortality. However, neutralization of IL-12 abrogated the development of disease in C3H/HeJ mice, demonstrating t hat activated macrophages and their products participated in the developmen t of SGVHD in these animals. These data suggested that LPS responsiveness w as not a predisposing factor for SGVHD induction.