Effect of methylprednisolone and of ibuprofen, a nonsteroidal antiinflammatory agent, on bronchoalveolar inflammation following endotoxemia.
Septicemia by gram-negative organisms is a common cause of the adult respiratory distress syndrome (ARDS). The role of neutrophils in causing parenchymal lung damage in ARDS has recently been emphasized. A single intraperitoneal injection of Escherichia coli endotoxin in rats causes acute neutrophil alveolitis similar to that of ARDS. We studied the ability of pretreatment with either ibuprofen (IBU) or methylprednisolone (MP) to ablate directly the alveolar inflammatory response to endotoxin in the rat model. To compare the severity of inflammation, we quantified inflammatory cell recovery by whole lung lavage 24 hours after injection of endotoxin, the time point at which neutrophil alveolitis due to endotoxin is most intense. Pretreatment with a single dose of IBU 3.75 mg/kg prior to endotoxin injections was associated with a significant increase in the total number of inflammatory cells, and in both the percentage and the absolute number of neutrophils recovered from the lung, despite significantly decreasing the plasma level of thromboxane B2, which increased 10-fold after endotoxin. Paradoxically, IBU 30 mg/kg significantly decreased the intensity of neutrophil alveolitis. MP 30 mg/kg had no effect on recovery of inflammatory cells from the lung by bronchoalveolar lavage following endotoxin. Cyclooxygenase inhibitors such as ibuprofen may cause a dose-dependent biphasic effect on lung inflammation following endotoxin: enhancement of inflammation at a low dose and suppression of inflammation at a high dose.
D000818:Animals; D001991:Bronchitis / Q000188:drug therapy* / Q000209:etiology; D006090:Gram-Negative Bacteria; D007052:Ibuprofen / Q000627:therapeutic use*; D007958:Leukocyte Count; D008775:Methylprednisolone / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology; D012772:Shock, Septic / Q000150:complications*; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D013929:Thromboxane B2; D007052:Ibuprofen; D008775:Methylprednisolone