Circadian fluctuations of melatonin, tumor necrosis factor-alpha and its soluble receptors in the circulation of patients with advanced gastrointestinal cancer.

The objective of the study was to investigate the dynamic changes of melatonin (MLT), tumor necrosis factor alpha (TNFalpha), soluble TNFalpha receptors ( type I and type II) in serum of advanced cancer patients during 24 hours. The examined group consisted of 42 patients suffering from advanced gastrointestinal neoplasms (colorectal, gastric and pancreatic cancer). Blood samples were collected 6 times a day (8 a.m., 2 p.m., 6 p.m., 10 p.m., 2 a.m., and again 8 a.m.) as well as in healthy controls. Serum levels of TNFalpha and both its receptors were measured using ELISA type and the radioimmunoassay method was used to assess MLT levels. The circadian rhythm of MLT was altered because MLT reached its peak level at 8.50 a.m. with 5 hours delay in respect to average peak time in healthy humans. The presence of circadian rhythm of TNFalpha was proved (acrophase-1.40 a.m.), and no diurnal rhythm of soluble TNF receptors was observed. The concentration of soluble type I (p-55) receptor was distinctly lower than soluble type II (p-75). The peak of soluble type I receptor value appeared at 10.00 p.m. while the type II receptor reached its minimum level at the same time. Although there was no statistical correlation between the receptor concentrations, the shapes of both curves remained inversely proportional. The present results may suggest the presence of complex self-regulation mechanisms between the neuroendocrine system and the cytokine network in advanced gastrointestinal cancer patients.