Role of prostaglandins in tumour necrosis factor induced weight loss.
Administration of either tumour necrosis factor alpha (TNF-alpha) or 16,16-dimethylprostaglandin E2 (PGE2) to female NMRI mice caused a decrease in body weight accompanied by a reduction in both food and water intake and a decrease in carcass water content. A single injection of TNF-alpha caused an enhanced production of PGE2 by spleen cells from treated animals, that was significant within 1 h of treatment, and persisted until at least 6 h. These results suggest that the anorectic effect of TNF-alpha may be mediated by a prostaglandin intermediate. Indomethacin (10 mg kg-1) administered 2 h before TNF-alpha (7.5 x 10(7) U kg-1) caused a significant reduction in the extent of weight loss and inhibited PgE2 production. Administration of indomethacin 0.5-1.5 h before the TNF-alpha had no significant effect on loss of body weight, but still inhibited PgE2 production. Also PgE2 production was still enhanced in response to TNF-alpha administered chronically, despite the inability of prolonged TNF-alpha administration to produce continued loss of body weight. These results suggest that prostaglandins are not involved in the anorectic effect of TNF-alpha.
Mahony
S M
SM
CRC Experimental Chemotherapy Group, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000502:physiology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015431:Weight Loss / Q000187:drug effects*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin