Inhibitory effects of interleukin-4 on human renal cell carcinoma cells in vitro: in combination with interferon-alpha, tumor necrosis factor-alpha or interleukin-2.
BACKGROUND
Immune cytokines have been shown to play important roles in regulating the growth of neoplastic cells, as well as the function of immune cells. The present study assessed the effects of interleukin (IL)-4 alone, and in combination with recombinant interferon (IFN)-alpha 2b, or with IL-2, or with tumor necrosis factor (TNF)-alpha on the in vitro proliferation of human renal cell carcinoma (RCC) cell-lines.


METHODS
Growth-inhibitory effects of IL-4 alone, and in combination with other cytokines, on three human RCC cell-lines, Caki-1, CURC-II, and A-498, were measured by the [3H]thymidine incorporation assay.


RESULTS
IL-4 inhibited proliferation of all three human RCC cell-lines (P < 0.001). The maximum growth inhibition of RCC cell-lines by IL-4 alone was observed at the concentration of 1 to 3 ng/mL, depending on the cell-line. Antihuman IL-4 antisera was able to reverse the growth-inhibitory effects of IL-4 on Caki-1 in a dose-dependent manner, proving that the growth inhibition was mediated by IL-4 itself. When other cytokines were added in combination with IL-4, only IFN-alpha 2b resulted in significant additional growth inhibition (P < 0.005). However, when the proliferation was compared to that of RCC cells that were not treated with any cytokine, all combinations produced marked growth inhibition.


CONCLUSIONS
Our data suggest that IL-4 alone, or in combination with IFN-alpha 2b, can be used to develop new strategies for treatment of human RCC.
Cheon
J
J
Department of Urology, Korea University College of Medicine, Seoul, Korea.
Chung
D J
DJ
Kim
J J
JJ
Koh
S K
SK
Sohn
J
J
D000918:Antibody Specificity; D016588:Anticarcinogenic Agents / Q000276:immunology / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D016207:Cytokines; D004338:Drug Combinations; D006131:Growth Inhibitors; D007106:Immune Sera; D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4