The effect of adrenaline and Walker-256 tumour-induced cachexia upon Kupffer cell metabolism

Kupffer cells (KC), the liver macrophages, are able to produce PGE2, which is involved in immune suppression and in the aggravation of cancer cachexia due to interference with lipid metabolism in the liver. Since tumour‐bearing (TB) rats present high plasma epinephrine levels, and this hormone is able to affect macrophage metabolism and function, we have assessed the effect of epinephrine (5 nm) upon Kupffer cell PGE2 production. Epinephrine induced increased production of PGE2 both by control (3·5‐fold) and TB rats (27 per cent) KC, an effect blocked by propranolol. Enhancement of cAMP content in the cells by addition of isoproterenol (0·1 μm) to the incubations, however, failed to induce the same response in the cells. Nevertheless, when phenylephrine (1 μm) was added to the incubation, a similar pattern of PGE2 production to that observed for epinephrine was found for control and TB rat KC. We propose that the effect of epinephrine upon KC PGE2 production is mediated by α‐adrenergic receptors and that Ca2+ is involved in the response, since increasing concentrations of the ion added to the incubation medium (0·25, 0·5 and 1·0 mm) enhanced the eicosanoid production, while EDTA abolished the response. Copyright © 1999 John Wiley & Sons, Ltd.