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

In addition to its efficacy in the treatment of chemotherapy-induced neutro penia, recent evidence would suggest that GM-CSF may have immunomodulatory effects on anticancer immunity. In particular, GM-CSF has been proven to pr omote dendritic cell maturation, with following potential stimulation of th e anticancer cytokine, IL-12. Unfortunately, at present there are only few and controversial results on GM-CSF effects on IL-12 secretion in cancer pa tients. This preliminary study was performed to evaluate IL-12 response to an acute injection of GM-CSF in human neoplasms. The study included 20 adva nced cancer patients, who received GM-CSF for chemotherapy-induced neutrope nia. 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 inje ction. Serum levels of IL-12 were measured by an enzyme immunoassay. High b asal levels of IL-12 were seen in 8/20 patients. In patients with abnormall y high pretreatment levels of IL-12, no significant change occurred in IL-1 2 mean serum concentration after GM-CSF administration. In contrast, patien ts 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-1 2 secretion in cancer patients. Further studies are required to evaluate th e effects of chronic GM-CSF administration, and the impact of GM-CSF-induce d 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 rese arch in the emerging oncological applications of GM-CSF as an immunomodulat ory agent on host anticancer defenses.