Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration

The adipose tissue (AT) is severely affected by cachexia, a paraneoplastic syndrome, which increases the morbidity and mortality of cancer. There is, however, a heterogeneous response to the condition, according to the AT depot. As plasma leptin concentration has been often reported to vary in cachexia, we have measured ( species specific radioimmunoassay) the local concentration of leptin in three AT depots: retroperitoneal (RPAT), epididymal (EAT) and mesenteric (MES) of Walker 256 tumour-bearing rats. A reduced concentration of leptin (P< 0.0001) was found in all the depots and in the plasma of the cachectic rats, compared with controls already from day 4 after tumour cell injection. The presence of a cell infiltrate was observed in all AT obtained from the tumour-bearing animals. Ultrastructural analysis, along with immunocytochemistry for RT1B (indicating the presence of MHCII) and using antibody against mononuclear phagocytes, showed the cells to be macrophages. The profile of TNF alpha and PGE(2) secretion by the infiltrate was investigated ( commercial kits). There was increased production of both factors by the cells of all AT ( P< 0.05) compared with peritoneal macrophages obtained from the cachectic rats, while the cells isolated from MES showed the highest synthesis of TNFalpha. The results suggest a possible modulation of the chronic locally produced TNFalpha and PGE(2) upon leptin synthesis by the AT of the cachectic rats.