Role of prostaglandins in tumour necrosis factor induced weight loss

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Abstract
Administration of either tumour necrosis factor alpha (TNF-.alpha.) or 16,16-demethylprostaglandin 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 .times. 107 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.