Anti-Macrophage Migration Inhibitory Factor Antibody Suppresses Chronic Rejection of Heterotopically Transplanted Trachea in Rats

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine essential for delayed hypersensitivity in vivo, and is involved in bronchiolitis obliterans and late rejection in lung transplantation. We tested here whether neutralization of MIF using anti-MIF antibody prevents such a response. We examined the MIF mRNA expression level and changes in allograft tracheal epithelium and intraluminal obstruction in a rat allograft model. Lewis rat (RT1l) underwent heterotopic tracheal transplantation from Brown Norway rats (RT1n) in the omentum. Anti-MIF antibody was injected in the peritoneum. Rats were divided into three groups (non-treated allograft, allograft treated with normal rabbit IgG and allograft treated with anti-MIF antibody). Implants were harvested on days 7 or 21 for histological analysis. MIF mRNA expression was higher in the allograft at days 7 and 21 than in the isograft. The epithelium in non-treated allograft was almost absent at day 7. The epithelial height in the anti-MIF-treated graft was higher than that in normal IgG-treated grafts. The intraluminal space was mostly replaced by granulation tissue at day 21 in the untreated group. The proportion of obliterans was lowest in the anti-MIF group, the second lowest in the untreated group and the third lowest in the normal IgG-treated grafts, and the difference was significant (p
Acta medica Nagasakiensia. 2006, 51(2), p.51-56