Tumor necrosis factor can induce fever in rats without activating protein breakdown in muscle or lipolysis in adipose tissue.
Tumor necrosis factor (TNF, cachectin) is a macrophage product that has been suggested to signal the loss of body weight, the decrease in adipose tissue and muscle mass, and anorexia during infections or chronic illness. To test this possibility, young growing rats were injected subcutaneously or intraperitoneally with human or murine recombinant TNF. After 3-4 h, these animals developed a 1-2 degrees fever which lasted approximately 4 h. With repeated daily TNF injections for 5 d, the animals developed fevers similarly each day. In contrast, rats injected with endotoxin show a single febrile episode and then are tolerant to subsequent daily injections of endotoxin (but do not develop tolerance to TNF or interleukin-1). On the first day of TNF treatment, the rats did not grow, but on subsequent days, despite their fevers, they grew at similar rates as controls. Although the TNF-treated rats consumed slightly less food than control animals, the ratio of growth per amount of food intake was identical in the two groups. When rats are administered endotoxin, they develop a fever, and their muscles show increased protein degradation and prostaglandin (PG)E2 production. However, when fevers were induced with TNF, there was no change in muscle proteolysis or PGE2 production, and in adipose tissue no increase in basal or catecholamine-induced lipolysis. Also TNF addition in vitro did not enhance lipolysis in epididymal fat pads or proteolysis in soleus muscles. Thus, TNF treatment can induce fever without producing a catabolic state similar to that induced by endotoxin.
Kettelhut
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Department of Physiology and Biophysics, Harvard Medical School, Boston, Massachusetts 02115.
Goldberg
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AL
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D015232:Dinoprostone; D004435:Eating; D005334:Fever / Q000139:chemically induced*; D008066:Lipolysis; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D009124:Muscle Proteins; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone