STIMULATION OF MUSCLE PROTEIN-DEGRADATION AND PROSTAGLANDIN-E2 RELEASE BY LEUKOCYTIC PYROGEN (INTERLEUKIN-1) - A MECHANISM FOR THE INCREASED DEGRADATION OF MUSCLE PROTEINS DURING FEVER
STIMULATION OF MUSCLE PROTEIN-DEGRADATION AND PROSTAGLANDIN-E2 RELEASE BY LEUKOCYTIC PYROGEN (INTERLEUKIN-1) - A MECHANISM FOR THE INCREASED DEGRADATION OF MUSCLE PROTEINS DURING FEVER
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DOI：
10.1056/nejm198303103081002
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发表时间：
1983-01-01
影响因子：
158.5
通讯作者：
GOLDBERG, AL
中科院分区：
文献类型：
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作者：
BARACOS, V;RODEMANN, HP;GOLDBERG, AL
为了阐明发热和脓毒症时机体蛋白质丢失的机制，将大鼠肌肉与高度纯化的人白细胞热原孵育。这种多肽与白细胞介素-1相同，由白细胞释放，并在下丘脑中发出发热的信号。在37 ℃孵育的肌肉中，白细胞致热原刺激蛋白质净降解62-118%（P < 0.001）。蛋白质水解增加，但肌肉蛋白质合成率没有变化。热原还极大地刺激了前列腺素[PG] E2的肌肉合成，这促进了该组织中的蛋白质分解。此外，吲哚美辛与白细胞热原阻止PG E2的合成，并取消增加蛋白水解。由热原诱导的蛋白质分解的加速也被溶酶体巯基蛋白酶抑制剂Ep-475阻断。当肌肉在39度下孵育时。C模拟发热，蛋白质分解增加，但白细胞热原的加入引起蛋白质水解和PGE 2产生的进一步显着增加。人白细胞热原可作用于骨骼肌，通过增加PGE 2的产生来刺激溶酶体内蛋白水解。环氧合酶抑制剂可用于治疗发热时的负氮平衡。白细胞致热原引起的PGE 2释放可能是伴随发热的肌痛的原因。
To clarify the mechanisms underlying the loss of body protein during fever and sepsis, rat muscles were incubated with highly purified human leukocytic pyrogen. This polypeptide, which appears identical to interleukin-1, is released by leukocytes and signals the onset of fever in the hypothalamus. In muscles incubated at 37.degree. C, leukocytic pyrogen stimulated net protein degradation by 62-118% (P < 0.001). Proteolysis increased, but rates of muscle-protein synthesis did not change. The pyrogen also dramatically stimulated muscle synthesis of prostaglandin [PG] E2, which promotes protein breakdown in this tissue. Addition of indomethacin with leukocytic pyrogen prevented PG E2 synthesis and abolished the increase in proteolysis. The acceleration of protein breakdown induced by pyrogen was also blocked by Ep-475, an inhibitor of lysosomal thiol proteases. When muscles were incubated at 39.degree. C to mimic fever, protein breakdown increased, but addition of leukocytic pyrogen caused a further marked increase in proteolysis and PGE2 production. Human leukocytic pyrogen can act on skeletal muscle to stimulate intralysosomal proteolysis by increasing the production of PGE2. Cyclooxygenase inhibitors may be useful in the treatment of negative nitrogen balance in fever. The release of PGE2 induced by leukocytic pyrogen may account for the myalgia that accompanies fever.