Stimulation of IL-12 secretion by GM-CSF in advanced cancer patients

• Published in: Journal of biological regulators and homeostatic agents Vol. 15; no. 2; p. 163
• Main Authors: Lissoni, P, Fumagalli, E, Malugani, F, Ardizzoia, A, Bucovec, R, Tancini, G, Gardani, G S
• Format: Journal Article
• Language: English
• Published: Italy 01.04.2001
• Subjects: Adjuvants, Immunologic - pharmacology; Adult; Aged; Antineoplastic Agents - adverse effects; Female; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Humans; Interleukin-12 - blood; Interleukin-12 - secretion; Kinetics; Male; Middle Aged; Neoplasms - drug therapy; Neoplasms - immunology; Neutropenia - chemically induced; Neutropenia - drug therapy; Recombinant Proteins
• ISSN: 0393-974X

In addition to its efficacy in the treatment of chemotherapy-induced neutropenia, recent evidence would suggest that GM-CSF may have immunomodulatory effects on anticancer immunity. In particular, GM-CSF has been proven to promote dendritic cell maturation, with following potential stimulation of the anticancer cytokine, IL-12. Unfortunately, at present there are only few and controversial results on GM-CSF effects on IL-12 secretion in cancer patients. This preliminary study was performed to evaluate IL-12 response to an acute injection of GM-CSF in human neoplasms. The study included 20 advanced cancer patients, who received GM-CSF for chemotherapy-induced neutropenia. GM-CSF was injected at 3 micrograms/kg at 8.00 A.M., and venous blood samples were drawn before GM-CSF, and at 4, 8, 12 and 24 hours after its injection. Serum levels of IL-12 were measured by an enzyme immunoassay. High basal levels of IL-12 were seen in 8/20 patients. In patients with abnormally high pretreatment levels of IL-12, no significant change occurred in IL-12 mean serum concentration after GM-CSF administration. In contrast, patients with normal baseline levels of IL-12 showed a significant increase in IL-12 mean concentrations in response to GM-CSF, with a peak after 12 hours. This preliminary study seems to show that GM-CSF may acutely stimulate IL-12 secretion in cancer patients. Further studies are required to evaluate the effects of chronic GM-CSF administration, and the impact of GM-CSF-induced secretion of IL-12 on the efficacy of the immunotherapies of cancer with cytokines, such as IL-2. In any case, this study would justify further research in the emerging oncological applications of GM-CSF as an immunomodulatory agent on host anticancer defenses.