Induction of syngeneic graft-versus-host disease in LPS hyporesponsive C3H/HeJ mice. |
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Authors: | D L Flanagan R Gross C D Jennings B E Caywood S Goes A M Kaplan J S Bryson |
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Affiliation: | Department of Microbiology and Immunology, Markey Cancer Center, University of Kentucky, Lexington 40536-0093, USA. |
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Abstract: | Syngeneic GVHD (SGVHD) develops following syngeneic bone marrow transplantation and treatment with cyclosporine A. Previous studies have demonstrated a role for IL-12, IFN-gamma, and TNF-alpha in the development of murine SGVHD. Macrophages can be activated to secrete IL-12 and TNF-alpha 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. |
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