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-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.
Flanagan
D L
DL
Department of Microbiology and Immunology, Markey Cancer Center, University of Kentucky, Lexington 40536-0093, USA.
Gross
R
R
Jennings
C D
CD
Caywood
B E
BE
Goes
S
S
Kaplan
A M
AM
Bryson
J S
JS
D000818:Animals; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000276:immunology* / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D014181:Transplantation Immunology; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016572:Cyclosporine