Involvement of cytokines in the mechanism of whole-body hyperthermia-induced cardioprotection.
BACKGROUND
Hyperthermia increases cardiac tolerance to ischemia/reperfusion injury and activates manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, in myocardium in a biphasic manner. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced a biphasic cardioprotection that corresponded to the activation of Mn-SOD. However, a direct association between Mn-SOD activation in myocardium and the acquisition of tolerance to ischemia/reperfusion injury induced by hyperthermia and the involvement of the cytokines in the signal transduction pathway for the hyperthermia-induced cardioprotection have not yet been elucidated.


RESULTS
Hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. At 0.5 and 72 hours after hyperthermia, ischemia was induced by occlusion of the left coronary artery for 20 minutes, followed by reperfusion for 48 hours. Inhibition of the increases in Mn-SOD content and activity 72 hours after hyperthermia by the administration of antisense oligodeoxynucleotides to Mn-SOD abolished the expected decrease in myocardial infarct size. The simultaneous administration of neutralizing antibodies to TNF-alpha and IL-1beta before hyperthermia abolished the biphasic cardioprotection and increase in Mn-SOD activity.


CONCLUSIONS
The increase in Mn-SOD activity mediated through the production of TNF-alpha and IL-1beta by whole-body hyperthermia is important in the acquisition of early- and late-phase cardioprotection against ischemia/reperfusion injury in rats.
Yamashita
N
N
First Department of Medicine, Osaka University Medical School and the Cardiovascular Division, Osaka, Japan.
Hoshida
S
S
Otsu
K
K
Taniguchi
N
N
Kuzuya
T
T
Hori
M
M
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004789:Enzyme Activation; D005334:Fever; D008297:Male; D015428:Myocardial Reperfusion Injury; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000502:physiology*
D016207:Cytokines; D013482:Superoxide Dismutase