Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies.
We have evaluated the synergistic effects of interleukin-1 (IL-1) and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) activity. Subcutaneous injection of recombinant IL-1 beta at an initial dose of 1 x 10(4) U was given to nine patients (five with renal cell carcinoma, two with bladder carcinoma, one with renal pelvic tumor, one with testicular tumor) on days 1 and 2 weekly for 4 weeks. The dose was increased weekly up to 4 x 10(4) U, if it was well tolerated. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in the 2nd and 4th weeks, and LAK activity of PBMC against Daudi cells was measured using a 4-h 51Cr-release assay at an effector:target cell ratio of 20:1, after incubation with 50 U/ml of recombinant IL-2 for 72 h. Proliferation of PBMC was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 h. IL-2 receptor (IL-2R)-positive cells in PBMC were enumerated using monoclonal antibody and flow cytometry. Mean values of LAK activity induced by IL-2 were significantly augmented after administration of IL-1 beta (p less than 0.01). IL-1 beta, however, did not enhance proliferation of PBMC caused by IL-2, nor did it increase the number of IL-2R-positive cells in peripheral blood lymphocytes of the patients. Results suggest that combination of IL-1 and IL-2 has synergistic antitumor activity in treatment of malignant diseases.
Marumo
K
K
Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
Tachibana
M
M
Deguchi
N
N
Tazaki
H
H
D002455:Cell Division / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014571:Urologic Neoplasms / Q000628:therapy*
D007155:Immunologic Factors; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins