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 disorder using an experimental rat model of cecal ligation and puncture (CLP). 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). Concentrations of endotoxin (ET) in arterial blood were significantly higher in the CLP + MP rats than in the CLP rats, while those in the bronchoalveolar lavage fluid (BALF) were significantly lower. Alveolar macrophages (AM) obtained from the CLP rats (CLP-AM) generated more O2-than did AM from sham-operated rats (sham-AM) following stimulation. However, the administration of MP did not reduce the upregulated generation of O2-by CLP-AM. While CLP-AM produced less leukotriene (LT)B4 than did sham-AM following stimulation with A23187, the administration of MP further reduced LTB4 production. When AM were cultured with [3H]arachidonic acid (3H-AA), the uptake of the isotope and the 3H release were significantly less in CLP-AM than in sham-AM. The administration of MP did not cause recoveries in the uptake and release of 3H-AA by CLP-AM. Although the survival time of CLP rats was significantly prolonged and the translocation of ET into BALF was reduced by steroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O2- and reduced LTB4 production from CLP-AM were not reversed by the treatment of this drug.
Abe
M
M
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
Goya
T
T
Mitsuyama
T
T
Torisu
M
M
Furukawa
T
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004731:Endotoxins / Q000097:blood / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D013256:Steroids / Q000627:therapeutic use*
D004731:Endotoxins; D013256:Steroids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D008084:Lipoxygenase; D008775:Methylprednisolone