1181 BACTERIAL ENDOTOXIN PROTECTION FROM PULMONARY OXYGEN TOXICITY

Abstract

We have discovered that treatment with small doses of bacterial lipopolysaccharide (endotoxin)(approx. 1/100th LD50) affords marked protection against O2-induced lung damage and lethality in adult rats exposed to hyperoxia. Whereas the untreated adult rat normally succumbs to 95+% O2 exposure after 72 hours(66/201= 30% survival) with survivors showing evidence of severe lung injury (pulmonary edema and/or hemorrhage), rats treated with daily i.p. doses of endotoxin exhibit tolerance to O2 lethality(265/274=97% survival) and lung damage (approx. 85% without evidence of pulmonary edema or hemorrhage). In addition to investigating possible mechanisms to explain the marked protective action of endotoxin treatment (↑lung antioxidant enzyme activity, p<.05; ↓ number of potentially detrimental alveolar macrophages, p<.05), preliminary attempts have been made to determine if endotoxin will offer similar protection from 02 toxicity in other species and other age animals. To date, endotoxin treatment appears to be protective only in the adult rat and rabbit(75% vs. 0% survival in 95+% 02). Initial experiments have been done in neonatal guinea pigs(55% vs. 13% survival, but only 18% free of lung pathology); neonatal hamsters(21% vs. 17% survival); and, adult mice(57% vs. 50% survival). Whether there is a true species(and/or age) specificity for endotoxin protection, or whether ideal dosage schedules in the other species have not yet been determined, remains to be resolved. (NIH# 1F 32 HL05415, GM 12675).