In vivo stimulation of IL-12 secretion by subcutaneous low-dose IL-2 in metastatic cancer patients.
Despite the well-demonstrated involvement of both interleukin 2 (IL-2) and interleukin 12 (IL-12) in the activation of host anti-cancer response, the knowledge of IL-2-IL-12 interactions has still to be better investigated. This study was performed to evaluate the effects of subcutaneous (s.c.) low-dose IL-2 on IL-12 secretion in metastatic cancer patients. The study included 19 evaluable metastatic renal cell cancer patients, who received s.c. low-dose IL-2 (6 MIU day(-1) for 6 days per week for 4 weeks) as a first-line immunotherapy of their metastatic disease. Serum levels of IL-12 were measured using an enzyme immunoassay on venous blood samples collected before the immunotherapy and at 1-week intervals. The clinical response consisted of partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 observed in the overall patients significantly increased in response to IL-2 injection. Moreover, by evaluating IL-12 variations in relation to the clinical response, a marked significant increase in IL-12 mean values occurred in patients with response or SD, whereas the progressing patients showed a significant decline in IL-12 levels during IL-2 administration. Finally, IL-12 mean pretreatment values observed in patients who progressed were significantly higher than those seen in non-progressing patients. This study shows that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo release of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is associated with a favourable prognosis.
Divisione di Radioterapia Oncologica, San Gerardo Hospital, Milan, Italy.
P
P
Lissoni
L
L
Fumagalli
F
F
Rovelli
F
F
Brivio
G
G
Di Felice
F
F
Majorca
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
D007376:Interleukin-2; D018664:Interleukin-12