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 anticancer response, the k nowledge of IL-2-IL-12 interactions has still to be better investigated. Th is study was performed to evaluate the effects of subcutaneous (s.c.) low-d ose IL-2 on IL-12 secretion in metastatic cancer patients. The study includ ed 19 evaluable metastatic renal cell cancer patients, who received s.c. lo w-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 meas ured using an enzyme immunoassay on Venous blood samples collected before t he immunotherapy and at I-week intervals. The clinical response consisted o f partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 obs erved in the overall patients significantly increased in response to IL-2 i njection. Moreover, by evaluating IL-12 variations in relation to the clini cal response, a marked significant increase in IL-12 mean values occurred i n patients with response or SD, whereas the progressing patients showed a s ignificant decline in IL-12 levels during IL-2 administration. Finally, IL- 12 mean pretreatment values observed in patients who progressed were signif icantly higher than those seen in non-progressing patients. This study show s that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo rele ase of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is a ssociated with a favourable prognosis.