Pretreatment with interleukin-2 modulates perioperative immunodysfunction in patients with renal cell carcinoma.

Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing nephrectomy. Here, the effect of pretreatment with IL-2 is addressed. Of 63 patients who underwent tumour nephrectomy, 26 patients received four doses of 10 Mio IE/m2 IL-2 b.d. s.c. (i.e. a total of 40 Mio IE/m2) a week before operation, 37 did not. Parameters of cellular and humoral immunity (differential blood count, T-cell markers CD2, CD3, CD4, and CD8, B-cell markers CD19 and CD20, monocyte markers CD13 and CD14, NK-cell marker CD16, activation markers CD25, CD26, CD69 and HLA-DR, and cytokines IL-1-receptor antagonist (IL-1RA), IL-2, soluble IL-2-receptor (sIL-2R), IL-6, IL-10, and TGFbeta) were measured in peripheral venous blood. Blood was drawn before IL-2, one day before and immediately after the operation, and on the 1st, 3rd, 5th, and 10th postoperative day. All patients showed postoperatively elevated leukocyte and granulocyte counts, and elevated serum levels of cytokines IL-6 and IL-10. T-cell and activation markers were decreased. However, all these alterations were less accentuated in patients who had been pretreated with IL-2. Monocyte counts and IL-2 and TGFbeta levels were decreased, but IL-1RA and sIL-2R levels were elevated in pretreated patients. IL-2-related toxicity was WHO grade I-II in all patients, grade III in one patient. The anaesthetic regimen had no measurable effect. IL-6 concentrations were higher in renal venous than in venous pool blood, indicating IL-6 production in the tumour in vivo. Tumour-specific survival was better in pretreated patients with tumours extending beyond the kidney. Pretreatment with IL-2 modulates perioperative immunodysfunction in patients undergoing tumour nephrectomy. This affects in particular T-cell-mediated immunity and levels of cytokines IL-10 and IL-6. The IL-2 application scheme used here was followed by distinct counter regulation including monocytes, IL-2, sIL-2R, IL-1RA and TGFbeta. Taken together, pretreatment with IL-2 may complement surgery in the treatment of patients with renal cell carcinoma, and may help close the therapeutic gap between neo-adjuvant and adjuvant immunotherapy.