EXPRESSION OF INTERLEUKIN-6 IN TUMOR-BEARING MICE WITH CYTOKINE DEPENDENT CACHEXIA

Increased production of IL-6 in tumor-bearing mice occured in a variet y of host-tissues including tumor tissue. Elevated IL-6 transcription in tumor-bearing mice occured in the tumor, liver, kidney and the smal l intestine, and was associated with increased concentration in the ci rculation of bioactive IL-6 of normal size (almost-equal-to 20 000 kDa ) in addition with two larger but biologically inactive serum fraction s containing immune-reactive IL-6. These inactive complexes were not e xplained by circulating inhibitor(s). The occurrence of differently si zed tumor and host-tissue IL-6 mRNAs were dependent on the subcellular location (nuclear, ribosomal, cytoplasm). the tissue type and the kin d of cellular stimulation. In tumor-tissue, IL-6 was produced to the h ighest concentration in tumor cells, followed by inflammatory and endo thelial cells respectively, but IL-6 did not seem to represent an auto crine growth factor loop as earlier reported by us for both IL-1alpha and TNFalpha in the present tumor model. In contrast, evidence support ed that IL-6 acted as a paracrinic factor in this model stimulated by some other host-derived factor(s).