GROWTH-INHIBITION OF HUMAN COLORECTAL-CARCINOMA CELLS BY INTERLEUKIN-4 AND EXPRESSION OF FUNCTIONAL INTERLEUKIN-4 RECEPTORS

The growth-inhibitory effect of interleukin-4 (IL-4) was investigated in a panel of 7 human colorectal-carcinoma cell lines. In 5 cell lines (HT29, WiDr, LS411N, LS513, LS1034) a dose-dependent reduction of pro liferation was documented. At 100 U/ml, IL-4 inhibited thymidine incor poration between 45 and 75% and MTT conversion (26 to 41%). The abilit y of LS513 and WiDr cells to form colonies after IL-4 treatment was re duced by 85 and 62% respectively. LS513 was the most sensitive cell li ne, with IL-4 inducing half-maximal inhibition at 5 to 6 U/ml. The inh ibitory effect of IL-4 was completely neutralized by anti-IL-4 antibod ies. Northern-blot analysis revealed the presence of IL-4-receptor (IL -4R) mRNA in all cell lines. The membrane expression of the 130-kDa IL -4R was assessed by FACS, utilizing an anti-IL-4R binding. Our results attribute an important role for IL-4 as a negative regulator of color ectal-carcinoma cell growth, thus indicating a possible avenue for int ervention in this disease. (C) 1994 Wiley-Liss, Inc.