Leptin is a recently identified
hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and
body weight. A number of proinflammatory
cytokines, such as
interleukin (IL) 1alpha,
IL-6,
tumor necrosis factor (
TNF) alpha and
interferon (IFN) gamma, have been proposed as mediators of
cancer cachexia. These data suggest that abnormalities in
leptin production/release or in its feedback mechanism play a role in
cancer patients. To elucidate this we studied the relationship between total serum
leptin and serum
cytokines IL-1alpha,
IL-6,
TNFalpha as well as the production of
leptin and
cytokines by peripheral blood mononuclear cells (PBMC) isolated from
cancer patients. Sixteen advanced
cancer patients (mainly stage IV) with
tumors at different sites were included in the study. The serum levels of
leptin in
cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL-1alpha,
IL-6, and
TNFalpha were significantly higher in
cancer patients than in healthy individuals. An inverse correlation between serum levels of
leptin and
IL-6 was found in
cancer patients. The production in culture of
leptin by unstimulated PBMCs and those stimulated by
phytohemagglutinin M or by
phorbol myristate acetate isolated from
cancer patients was very low; no differences were observed in comparison with
leptin production by PBMCs from healthy individuals.