Preliminary study on modulation of the biological effects of tumor necrosis factor-alpha in advanced cancer patients by the pineal hormone melatonin.
Previous experimental studies have suggested the possibility to modulate the biological activity and toxicity of cytokines by immunomodulating neurohormones. In particular, the pineal hormone melatonin (MLT) has been proven to amplify the immune effects of IL-2 and to reduce its toxicity. On this basis, we decided to investigate the effect of MLT on biological activity and toxicity of another important antitumor cytokine, TNF. The study was performed in 14 metastatic solid tumor patients, for whom no effective standard antitumor therapy was available. Informed consent was previously obtained from each patient. Patients were randomized to be treated with TNF or TNF plus MLT. Recombinant human TNF was given at a daily dose of 0.75 mg intravenously for 5 consecutive days. MLT was given orally at a daily dose of 40 mg, starting 7 days before TNF. Lymphocyte mean number observed at the end of TNF infusion was significantly higher in patients treated with TNF plus MLT than in those receiving TNF alone. On the contrary, no significant difference occurred in hemoglobin, platelet and neutrophil mean values. Asthenia and hypotension were significantly less frequent in patients treated with TNF plus MLT, whereas no difference occurred in the frequency of fever and chills. Even though limited to a small number of patients, this preliminary study would suggest the possibility to modulate TNF toxicity and biological activity by a concomitant treatment with the pineal hormone MLT.
Brackowski
R
R
Silesian University School of Medicine, Bytom, Poland.
Zubelewicz
B
B
Romanowski
W
W
Lissoni
P
P
Barni
S
S
Tancini
G
G
Maestroni
G J
GJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D005334:Fever; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D006801:Humans; D018655:Lymphocyte Count / Q000187:drug effects; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects; D010870:Pineal Gland / Q000737:chemistry; D012768:Shivering; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006454:Hemoglobins; D014409:Tumor Necrosis Factor-alpha; D008550:Melatonin