EVALUATION OF THE EFFECTS OF STEROIDS ON EXPERIMENTAL SEPTIC LUNG INJURY

To evaluate the clinical usefulness of steroids for septic lung injury , we investigated the effects of methylprednisolone (MP) on this disor der using an experimental rat model of cecal ligation and puncture (CL P). While 92% of the rats that underwent CLP (CLP rats) died within 30 h, those given high-dose MP (30 mg/kg) just after the operation (CLP + MP rats) survived for a significantly longer period (p < 0.01). Conc entrations of endotoxin (ET) in arterial blood were significantly high er in the CLP + MP rats than in the CLP rats, while those in the bronc hoalveolar lavage fluid (BALF) were significantly lower. Alveolar macr ophages (AM) obtained from the CLP rats (CLP-AM) generated more O-2(-) than did AM from sham-operated rats (sham-AM) following stimulation. However, the administration of MP did not reduce the upregulated gener ation of O-2(-) by CLP-AM. While CLP-AM produced less leukotriene (LT) B-4 than did sham-AM following stimulation with A23187, the administra tion of MP further reduced LTB(4) production. When AM were cultured wi th [H-3]arachidonic acid (H-3-AA), the uptake of the isotope and the H -3 release were significantly less in CLP-AM than in sham-AM. The admi nistration of MP did not cause recoveries in the uptake and release of H-3-AA by CLP-AM. Although the survival time of CLP rats was signific antly prolonged and the translocation of ET into BALF was reduced by s teroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O-2(-) and redu ced LTB(4) production from CLP-AM were not reversed by the treatment o f this drug.