Influence of endotoxin on graft-versus-host disease after bone marrow transplantation across major histocompatibility barriers in mice.
Much clinical and experimental data suggest that infection and graft-versus-host disease (GVHD) are intimately associated, and that bacterial endotoxin (ET), a potent immunostimulant, influences the severity of GVHD. We have used a cell-wall-deficient mutant of Escherichia coli (E coli J5) to study the effect of active and passive immunization against ET in a murine model of GVHD induced by major histocompatibility antigens. CBA/Ca (H-2k) mice were irradiated and grafted with 1 X 10(7) bone marrow cells from C57BL/B6 (H-2b) donors. Groups of mice were immunized against J5: either actively immunized with killed J5 cells or pure J5 lipopolysaccharide, or passively immunized with rabbit anti-J5 antiserum (R alpha J5). Controls included irradiation controls, negative controls (syngeneic graft), positive controls (conventional mice receiving allogeneic graft), mice immunized with normal rabbit serum, Freund's adjuvant (FA), or human serum albumin (HSA) in FA. Active immunization with J5 exacerbated the effects of GVHD as indicated by increased weight loss (P = 0.002) and earlier death (P = 0.043). In contrast, immunization with HSA protected against weight loss (P = 0.028), and improved survival (P = 0.008). Passive immunization with J5 had no effect. These observations support the hypothesis that ET influences the pathogenesis of GVHD, and provide a useful model for studying the effects of ET in a well-defined immunological system.