Stimulation of IL-12 secretion by GM-CSF in advanced cancer patients.
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.
Lissoni
P
P
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milano, Italy.
Fumagalli
E
E
Malugani
F
F
Ardizzoia
A
A
Bucovec
R
R
Tancini
G
G
Gardani
G S
GS
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor