PERTURBATIONS OF TRIGLYCERIDES BUT NOT OF CHOLESTEROL-METABOLISM ARE PREVENTED BY ANTITUMOR NECROSIS FACTOR TREATMENT IN RATS BEARING AN ASCITES HEPATOMA (YOSHIDA AH-130)

Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely progressive cachexia, characterised by marked alterations in protein and lipid metabolism. In particular, high levels of serum tri glycerides and free fatty acids were associated with altered levels an d distribution of plasma cholesterol, with increased total and very lo w-density lipoprotein-low-density lipoprotein (VLDL-LDL) cholesterol a nd reduced high-density lipoprotein (HDL) cholesterol. The tumour cell s showed high rates of cholesterol synthesis and elevated content of f ree and esterified cholesterol, whereas total cholesterol synthesis wa s reduced in the host liver. To determine whether these perturbations could be related to the elevation of tumour necrosis factor alpha (TNF alpha) previously shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J Cancer, 67, 15-23), either anti-TNF polyclona l antibodies or non-immune IgGs were injected daily after tumour trans plantation. The anti-TNF treatment neither affected tumour growth nor prevented the serum cholesterol changes, while attenuating the hypertr iglyceridaemia and the elevated serum free fatty acid levels. These da ta indicate that TNF does not appear to be directly involved in the al tered cholesterol metabolism in AH-130 hosts, thus supporting the view that cholesterol metabolism and lipid metabolism are regulated differ ently during tumour growth.