Induction of weight loss and metabolic alterations by human recombinant tumour necrosis factor

A comparison has been made of the weight loss produced by tumour necrosis factor (TNF) (cachectin) with that produced by a restricted food and water intake (pair-fed controls), and by mitozolomide, a drug which in toxic doses induces weight loss with a similar decrease in nutrient and water intake. When administered as two separate injections over a 24 h period (acute administration) TNF produced a dose-related weight reduction that was accompanied by and directly proportional to a decrease in both food and water intake. When administered daily by i.v. injection over a 5-day period (chronic administration) the major weight loss was found to occur during the first 24 h after injection and thereafter the weight of treated mice increased toward that of controls. Acute administration of TNF produced hypoglycaemia that was more severe than observed with either mitozolomide or in pair-fed controls, a reduction in the circulatory level of free fatty acids (FFA) and an increase in plasma triglycerides, while mitozolomide and pair-feeding had no effect on the level of blood glucose or plasma triglycerides. Body composition analysis showed a loss of adipose tissue in TNF-injected and pair-fed animals after both acute and chronic treatment. Acute administration of TNF also induced a decrease in the total body water content of treated animals which was similar to pair-fed controls. It is concluded that the weight loss produced by TNF arises from a combination of semi-starvation and a reduced water intake, and that the effect only occurred with the first administration of TNF.