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

Syngeneic GVHD (SGVHD) develops following syngeneic bone marrow transplantation and treatment with cyclosporine A. Previous studies have demonstrated a role for IL‐12, IFN‐γ, and TNF‐α in the development of murine SGVHD. Macrophages can be activated to secrete IL‐12 and TNF‐α via a T‐cell‐dependent 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. Following 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 that activated macrophages and their products participated in the development of SGVHD in these animals. These data suggested that LPS responsiveness was not a predisposing factor for SGVHD induction.