Abstract
Background and Aims : We examined whether the lung injury produced in rats by intravenous injection of TNF-α could be inhibited by the intravenous administration of human urinary trypsin inhibitor (UTI), since the results of previous investigations showed the ability of UTI to bind bacterial toxins and superantigen, to markedly inhibit serum TNF-α production, and reduce myeloperoxidase content of rat lungs.
Methods : The rats were infused with PBS, TNF-α (100 or 250 ng/rat) or UTI-TNF-α, through the rat tail vein under Nembutal anaesthesia. All lungs were then excised in individual experimental groups 5 h after the infusion, and examined histologically, histochemically and biochemically.
Results : Intravenous injection of TNF-α caused punctate areas of haemorrhage on the lung surface. Histological, histochemical and ultrastructural examinations revealed lung injuries of different extents, vasculitis with concentration of inflammatory cells, and infiltration of numbers of eosinophils around the arteries and veins of the pulmonary lobules and bronchioles. These morphological presentations were similar to those induced by intraperitoneal injection of the superantigen, staphylococcal enterotoxin B. However, the administration of UTI markedly attenuated the lung injuries and vasculitis induced by intravenous injection of TNF-α, involving a marked reduction in the number of inflammatory cells, infiltration of eosinophils, the extent of injury and myeloperoxidase content of rat lungs.
Conclusions : Taken together, UTI may have defensive effects on inflammation and/or infection by suppressing the early responses of stimulated cells.
