Effects of IL-2 preoperative immunotherapy on surgery-induced changes in angiogenic regulation and its prevention of VEGF increase and IL-12 decline.
OBJECTIVE
IL-2 preoperative immunotherapy has been proven to abrogate surgery-induced immunosuppression in cancer patients. In contrast, at present there are no data about the possible influence of IL-2 on angiogenesis-related molecular changes determined by the surgical operation. At present, it is known that VEGF (vascular endothelial growth factor) is the main endogenous angiogenic factor, whereas the antitumor cytokine IL-12 has appeared to play an anti-angiogenetic role. On this basis, a study was planned to evaluate the influence of IL-2 presurgical immunotherapy on the perioperative changes in VEGF and IL-12 secretions.


METHODS
The study was performed on 30 colorectal cancer patients undergoing radical surgery, who were randomly chosen to be treated with or without preoperative immunotherapy of IL-2 (12 million IU/day subcutaneously for 3 consecutive days prior to surgery). Serum levels of VEGF and IL-12 were measured by ELISA for blood samples collected before surgery, and at days 3, 7 and 10 of the postoperative period.


RESULTS
VEGF mean concentrations progressively and significantly increased during the postoperative period in patients treated with surgery alone. Mean values of VEGF were enhanced also in patients pretreated with IL-2, but VEGF increase observed in the IL-2 group was delayed, more transient and significantly lower with respect to that found in controls. IL-12 mean concentrations significantly decreased during the postoperative period only in the control patients, whereas in the IL-2-treated patients IL-12 postoperative mean values were not significantly lower than those found before surgery.


CONCLUSIONS
This preliminary study would suggest that IL-2 preoperative immunotherapy may abrogate surgery decline in IL-12 levels and reduce, although not completely prevent, VEGF increase during the postoperative period in surgically treated cancer patients. These results would suggest that IL-2 presurgical immunotherapy may counteract surgery-induced stimulation of the angiogenesis, by either opposing the decline in blood levels of the anti-angiogenetic cytokine IL-12, or reducing the increase in those of the angiogenic factor VEGF.
Brivio
Fernando
F
3rd Division of General Surgery, Surgery Clinic of 2nd University of Milano Bicocca, San Gerardo Hospital, Monza, Milano, Italy.
Lissoni
Paolo
P
Rovelli
Franco
F
Nespoli
Angelo
A
Uggeri
Franco
F
Fumagalli
Luca
L
Gardani
Gianstefano
G
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000601:surgery*; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000276:immunology*; D012004:Rectal Neoplasms / Q000276:immunology* / Q000601:surgery*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018664:Interleukin-12