Pretreatment with Interleukin-2 Modulates Peri-Operative Immuno-Dysfunction in Patients with Renal Cell Carcinoma

• Published in: European urology 2002-04, Vol.41 (4), p.458-468
• Main Authors: Böhm, M., Ittenson, A., Schierbaum, K.F., Röhl, F.-W., Ansorge, S., Allhoff, E.P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; B-Lymphocytes; Biomarkers, Tumor - blood; CAM; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - surgery; Complementary and alternative medicine; Female; Humans; Immune system; Immuno-dysfunction; Immuno-modulation; Interleukin-2; Interleukin-2 - therapeutic use; Kidney cancer; Kidney Neoplasms - blood; Kidney Neoplasms - drug therapy; Kidney Neoplasms - immunology; Kidney Neoplasms - surgery; Male; Middle Aged; Nephrectomy; Premedication; T-Lymphocytes
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/S0302-2838(02)00031-3

Objective: Complex peri-operative immuno-dysfunction occurs in patients with renal cell carcinoma undergoing nephrectomy. Here, the effect of pretreatment with interleukin-2 (IL-2) is addressed. Methods: Of 63 patients who underwent tumor nephrectomy, 26 patients received 4 doses of 10 Mio IE/m 2 IL-2 b.d. s.c. (i.e . a total of 40 Mio IE/m 2) 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 (natural killer)-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 TGFβ) were measured in venous blood. Blood was drawn before IL-2, 1 day before and immediately after the operation, and on the 1st, 3rd, 5th, and 10th postoperative day. Results: 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 TGFβ levels were decreased, but IL-1RA and sIL-2R levels were elevated in pretreated patients. IL-2 related toxicity was WHO grades I–II in all patients, grade III in one patient. The anesthetic regimen had no measurable effect. IL-6 concentrations were higher in renal venous than in venous pool blood, indicating IL-6 production in the tumor in vivo. Conclusions: Pretreatment with IL-2 modulates peri-operative immuno-dysfunction in patients undergoing tumor nephrectomy. This affects in particular T-cell-mediated immunity and levels of cytokines IL-10 and IL-6. The IL-2 administration scheme used here was followed by distinct counter-regulation including monocytes, IL-2, sIL-2R, IL-1RA and TGFβ.