LUNG INFLAMMATION IN MICE EXPOSED TO AEROSOLIZED ENDOTOXIN AND ITS REVERSAL BY ANTIPHLOGISTIC AGENTS

Abstract

A uniform lung inflammation was produced in mice by two exposures, 18 hours apart, to an aerosol of Salmonella abortus equi endotoxin. The inflammation reached a peak in 4 days and could be reversed by the subcutaneous or oral administration of steroidal or non-steroidal antiphlogistic agents on the second and third days. The anti-inflammatory potencies of the test compounds were determined by dose-proportional reductions in lung weights. The potencies of various anti-inflammatory steroids, relative to cortisone acetate, following subcutaneous administration were: dexamethasone, 539%; triamcinolone, 158%; methyl prednisolone, 100%; hydrocortisone acetate, 47%; cortisone, 33%; and hydrocortisone, 28%. Neither an antihistamine, an antiserotonin, nor sex steroids reversed the effects of endotoxin on the lungs. This new method offers several distinct advantages over established tests: the activities obtained reflect therapeutic, rather than preventive effectiveness since a state of inflammation exists at the time treatment is started; reversal of inflammation is easily verified by histological methods; and the test is rapid enough (4 days) for large-scale screening, yet sufficiently precise for quantitative assay.