INHIBITORY EFFECT OF LOCALLY PRODUCED AND EXOGENOUS INTERLEUKIN-6 ON TUMOR-GROWTH IN-VIVO

In order to define the potential antitumor activity of the multifuncti onal cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the mu rine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, the y were found to exhibit greatly reduced tumorigenicity in vivo followi ng intravenous injection into syngeneic recipients. Exogenous b IL-6 w as shown to produce a similar inhibition of tumor growth in the lung i f administered intraperitoneally. In contrast, tumor growth in subcuta neous sites was inhibited only if the tumor cells were engineered to e xpress IL-6 locally, or if IL-6 was administered intratumorally. Intra peritoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites wer e found to contain large numbers of macrophages. These results demonst rate that the antitumor activity of systemically administered IL-6 var ies depending on the site of tumor growth and suggest an important rol e for IL-6 in the recruitment, proliferation and/or survival of tumor- associated macrophages.