Prolonged lung edema formation during the generalized Shwartzman reaction in rabbits--can it be a model for septic lung disease?

Pulmonary edema formation and the role of polymorphonuclear leukocytes (PMN) was evaluated during the generalized Shwartzman reaction (GSR) model in rabbits. Chemiluminescence (CL) and superoxide (O2-) production activity stimulated by FMLP were measured in circulating PMN after a single intravenous injection of endotoxin (E. coli 026:B6, 40 micrograms/kg) (E1). CL peaked at 36 hr after E1 injection and then decreased gradually to a normal range within 7 days. O2- production changed in a similar fashion. On the other hand, the PMN count peaked at 72 hr and remained at a high value until day 7. To induce GSR, a second venous injection of endotoxin (40 micrograms/kg) (E2) was administered 36 hr after the first one (E1). Four times as many PMN were observed in the lung capillaries 4 hr after the second endotoxin injection than after the first endotoxin injection (4 hr). The degree of lung edema formed increased after E2, but did not increase after E1. An alveolar hyaline-like exudate was observed 24 hr after E2. A continuous intravenous injection of superoxide dismutase (SOD) plus catalase or PMN depletion, prevented the development of post-E2 lung edema. If E2 was given 7 days after E1, no lung edema formed at all. These data indicate that oxygen free radicals from activated PMN by endotoxin play an important role in prolonged lung edema formation in the GSR model.