Indomethacin blocks the anorexic action of interleukin-1

Uehara, Akira; Ishikawa, Yuji; Okumura, Toshikatsu; Okamura, Kiyoshi; Sekiya, Chihiro; Takasugi, Yuichi; Namiki, Masayoshi

doi:10.1016/0014-2999(89)90546-3

Cited by 84 publications

(24 citation statements)

References 10 publications

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“…However, the chain of physiological events that leads from increased secretion of IL-1 to the behavioral response has not yet been established. Ample evidence indicates that COX inhibitors attenuate the effects of IL-1 (McCarthy et al, 1986;Hellerstein et al, 1989;Uehara et al, 1989;Crestani et al, 1991;Bluthé et al, 1992;Shimomura et al, 1992;Langhans et al, 1993;Swiergiel et al, 1997a;Dunn and Swiergiel, 2000). COX inhibitors are somewhat less effective in preventing the hypophagic effects of LPS (Langhans et al, 1993;Johnson and von Borell, 1994;Swiergiel et al, 1997a).…”

Section: Discussionmentioning

confidence: 99%

Distinct Roles for Cyclooxygenases 1 and 2 in Interleukin-1-Induced Behavioral Changes

Świergiel

Dunn²

2002

J Pharmacol Exp Ther

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Interleukin-1 (IL-1) induces hypophagia, which can be reduced by cyclooxygenase (COX) inhibitors. Earlier studies with COX knockout (COXko) mice suggested that COX2 was more important for hypophagia than COX1. However, behavioral responses occur long before COX2 is induced. Hypophagia was assessed in mice by measuring the intake of sweetened milk in a brief period. The intake was reduced within 30 min after intraperitoneal injection of IL-1␤ and was depressed for about 2 h. When milk intake was measured 30 to 40 min after IL-1␤, COX1ko mice showed an attenuated response, whereas COX2ko mice responded more like wild-type animals. By contrast, 90 to 120 min after IL-1␤ COX1ko mice responded normally, whereas COX2ko mice showed only small responses. The COX2-selective inhibitor, celecoxib, failed to alter the response to IL-1␤ 30 min after administration, but low doses antagonized the effects of IL-1␤ at 90 to 120 min. The COX1-selective inhibitor, SC560, attenuated both the early and late responses, but a larger effect at 30 min than at 90 min suggested a role for COX1 at the earlier time. These results suggest that shortly after IL-1␤ administration, COX1 is the major enzyme involved in the reduction of milk intake, whereas at later times COX2 is more important, paralleling its induction. Celecoxib also attenuated the milk intake response observed 2 h after lipopolysaccharide (LPS), and the reductions of food pellet intake and body weight induced by IL-1␤ and LPS in the subsequent 24 h, suggesting that the role of COX2 may be more significant biologically than that of COX1.

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Section: Discussionmentioning

confidence: 99%

Distinct Roles for Cyclooxygenases 1 and 2 in Interleukin-1-Induced Behavioral Changes

Świergiel

Dunn²

2002

J Pharmacol Exp Ther

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“…However, data from other laboratories suggest that cytokines act on peripheral tissues (14,15). Several hormones known to regulate appetite, including corticotropin releasing hormone, cholecystokinin, prostaglandins, glucagon, insulin, and corticosteroids are induced by LPS and cytokines (8,(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.

Grünfeld¹,

Zhao²,

Fuller³

et al. 1996

J. Clin. Invest.

821

537

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The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin expression decreases during fasting. Infusion of leptin decreases food intake. Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection. Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters. In fasted animals, LPS increased the expression of leptin mRNA in adipose tissue to levels similar to fed control animals. There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake. TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin mRNA in adipose tissue. As assessed by immunoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA. Induction of leptin during the host response to infection may contribute to the anorexia of infection. (J. Clin. Invest. 1996. 97:2152-2157.)

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“…Indomechacin has been shown to attenuate cachectic events and decrease parameters and mediators of inflammation in animal models of cancer cachexia (19,27,28). However, indomethacin itself stimulates SSAT activities (29).…”

Section: Discussionmentioning

confidence: 99%

“…In cachectic mice bearing the clone 20 tumor, the non-significant decrease in the amount of phosphorylated ACC in spite of the significant decrease in the total ACC amount indicates an increased phosphorylation of ACC. The administration of several pro-inflammatory cytokines profoundly decreases the food intake of animals (19)(20)(21)(22), however direct evidence of the inhibitory activities of such cytokines on ACC is sparse. Therefore, the decreased ACC levels are likely due to the anorexia provoked by the factors involved in the pathogenesis of cachexia, while the direct effect of unknown factor(s) is undeniable.…”

Section: Discussionmentioning

confidence: 99%

Decrease in malonyl-CoA and its background metabolic alterations in murine model of cancer cachexia

Çelik

Kano²,

Tsujinaka³

et al. 2009

Oncol Rep

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Abstract. The alterations of enzymatic activities involved in lipid degradation in cancer cachexia have not been fully elucidated. One of the two subclones of colon 26 adenocarcinoma, clone 20, with a potent ability to induce cachexia, or clone 5, without such an activity, was transplanted in to CDF-1 male mice. Murine livers were extirpated for analyses on the 14th day after tumor inoculation. The body weights and food intake of mice bearing clone 20 were all significantly lower than those of non-tumor bearing mice and mice bearing the clone 5 tumor. The decline of body weight was accompanied by a shrinkage of epididymal fat pads. Expression of spermidine/spermine N-1 acetyl transferase (SSAT) assessed by real-time PCR was significantly increased in cachectic mice. Conversely, acetyl-CoA carboxylase (ACC) measured by Western blotting and malonyl-CoA levels determined by malonyl-CoA:acetyl-CoA cycling procedures were decreased in cachectic mice. Indomethacin in drinking water reversed the clone 20 induced decrease in body and fat weight and food intake, and simultaneously negated the clone 20 induced increase of SSAT expressions and decrease of ACC and malonyl-CoA amounts. Because malonyl-CoA inhibits the rate-limiting step in the beta-oxidation of fatty acids, the decreased malonyl-CoA and the background metabolic alterations may contribute to the accelerated lipolysis of cancer cachexia.

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Indomethacin blocks the anorexic action of interleukin-1

Cited by 84 publications

References 10 publications

Distinct Roles for Cyclooxygenases 1 and 2 in Interleukin-1-Induced Behavioral Changes

Distinct Roles for Cyclooxygenases 1 and 2 in Interleukin-1-Induced Behavioral Changes

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.

Decrease in malonyl-CoA and its background metabolic alterations in murine model of cancer cachexia

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