SHIBAMOTO Toshishige SHINSHU UNIVERSITY SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (90178921)
HONDA Takayuki SHINSHU UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (80238815)
KOIZUMI Tomonobu SHINSHU UNIVERSITY HOSPITAL,ASSISTANT, 医学部附属病院, 助手 (20273097)
FUJIMOTO Keisaku SHINSHU UNIVERSITY HOSPITAL,ASSISTANT, 医学部附属病院, 助手 (70242691)
KOBAYASHI Toshio SHINSHU UNIVERSITY HOSPITAL,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (80020775)
松沢 幸範 信州大学, 医学部・附属病院, 助手 (40219423)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
We investigated effects of JTE-607, a synthetase inhibitor of cytokines, especially tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) -1 and IL-6, on endotoxin-induced lung dysfunction in awake sheep with chronic lung lymph fistula. The pretreatment of JTE-607 (10mg/kg) did not prevent the dysfunctions induced by intravenous infustion of E.coli endotoxin (1 mug/kg) including pulmonary hypertension, circulating leukocyte depletion and hypoxemia during the early phase, and increased permeability edema during the late phase. The endotoxemia led to a significant increase in the serum concentration of TNF-alpha which was measured by bioassay (Yoshie et al.J Biochem 100 : 531,1986), but JTE-607 did not suppress the increased TNF levels.
Since secretary leukoprotease inhibitor (SLPI), which is a 12KDa serine antiproteasae and physiologically exist in the epithelial surface of upper airways significantly increases the levles of glutathione of lung epithelial lining layr and lung lymph i
n sheep (Gillissen et al.J Appl Physiol 75 : 825,1993), we tried the effects of recombinant half-sized SLPI (1/2 SLPI ; TEI-7361) on the levels of glutathione in bronchoalveolar lavage fluid (BALF) and lung lymph in awake sheep. Intravenous administration of TEI-7361 of 15mg/kg into awake sheep did not change the glutathione levels in BALF,lung lymph and serum. Therefore, it seems that 1/2 SLPI does not have the ability to increase the levels of glutathione of lung epithelial lining layr.
High altitude pulmonary edema (HAPE) is a non cardiogenic pulmonary edema, a typical disorder as acute lung injury, occurs in the Japan Alps. The pathogenesis of HAPE is unclear. We investigated the levels of ILs, TNF-alpha and P-selectin in BALF performed at early period of 7 patients with HAPE and the relations between these values and pulmonary hemodynamics. The proinflammatory cytokines such as IL-1 beta, IL-6, IL-8 and TNF-alpha were remarkably increased, but IL-10 and P-selection did not increase. However, these values were not detected or within low levels in BALF at recovery. The increased levels of IL-6 and TNF-alpha were related to driving pressure. The proinflammatory cytokines play an important role of the development of HAPE,although the role is transient. Furthermore, pulmonary hypertension is related to the changes of proinflammatory cytokines. On the other hand, we measured the levels of vascular endothelial growth factor (VEGF), a new chemotactic factor related to increasing permeability, in BALF at its early period of HAPE.The values were increased, but we need further studies to see the role of VEGF in HAPE. Less