Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis.
We have compared the role of tumor necrosis factor (TNF) in the pathogenesis of analogous acute immune complex-induced lung and dermal vascular injury models in rats. Intratracheal administration of IgG anti-bovine serum albumin (BSA), followed immediately by intravenous infusion of BSA, results in acute neutrophil-mediated alveolitis. Neutralization of intrapulmonary TNF activity with anti-TNF antibodies resulted in reduced pulmonary neutrophil recruitment and marked attenuation of lung injury. Intradermal injection of IgG anti-BSA, followed by intravenous BSA, results in acute neutrophil-mediated dermal vasculitis. Neither locally nor systemically administered anti-TNF antibodies reduced dermal vascular injury as measured by local hemorrhage and vasopermeability changes. Based on morphometric analysis and measurements of myeloperoxidase in tissue extracts, anti-TNF antibodies had no effect on dermal neutrophil recruitment. Intradermal and intrapulmonary administration of physiologic concentrations of recombinant human TNF resulted in modest, dose-dependent increases in local vasopermeability accompanied by negligible neutrophil recruitment. Administration of higher concentrations of TNF resulted in increases in both local vasopermeability and neutrophil recruitment. These data suggest that while both rat pulmonary and dermal blood vessels can respond to TNF-triggered proinflammatory events, endogenous TNF plays a much greater role in acute alveolitis than in dermal vasculitis.
Warren
J S
JS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
D000208:Acute Disease; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001183:Arthus Reaction; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D011014:Pneumonia / Q000209:etiology*; D051381:Rats; D012871:Skin Diseases / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*; D014657:Vasculitis / Q000209:etiology*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha