Effect of tacrolimus on endotoxin-induced lung injury in sheep.
Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.
Hanaoka
Masayuki
M
First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. masayuki@hsp.md.shinshu-u.ac.jp
Ge
Ri-Li
RL
Kaneki
Toshimichi
T
Koizumi
Tomonobu
T
Kobayashi
Toshio
T
Kubo
Keishi
K
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D012756:Sheep; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
D004731:Endotoxins; D016559:Tacrolimus