Pretreatment with interleukin-2 modulates peri-operative immuno-dysfunction in patients with renal cell carcinoma.
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 TGFbeta) 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 TGFbeta 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 TGFbeta.
Böhm
M
M
Department of Urology, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany. malte.boehm@medizin.uni-magdeburg.de
Ittenson
A
A
Schierbaum
K F
KF
Röhl
F-W
FW
Ansorge
S
S
Allhoff
E P
EP
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D014408:Biomarkers, Tumor / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011292:Premedication; D013601:T-Lymphocytes
D014408:Biomarkers, Tumor; D007376:Interleukin-2