Am. J. Respir. Crit. Care Med.,
Volume 163, Number 1, January 2001, 79-84
Pretreatment with FK506 Improves Survival Rate and
Gas Exchange in Canine Model of Acute Lung Injury
TADATSURA
KOSHIKA,
AKITOSHI
ISHIZAKA,
ITSUO
NAGATOMI,
YUJI
SUDO,
NAOKI
HASEGAWA,
and
TOSHIO
GOTO
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Company, Osaka, and Department of Medicine, School of Medicine,
Keio University, Tokyo, Japan
The novel effects of FK506 on shock induced by lipopolysaccharide
and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both
0.5 mg/kg of LPS and 30 µg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 µg/kg/h (low dose, n = 5), 8 µg/kg/h (medium dose, n = 5), and
25 µg/kg/h (high dose, n = 5) were administered. In the control
group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed.
FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA-induced physiological changes, and the
survival rates were 80 and 100%, respectively. On the other hand,
in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock.
