Expression of interleukin-6 in tumor-bearing mice with cytokine dependent cachexia

Increased production of IL-6 in tumor-bearing mice occured in a variety of host-tissues including tumor tissue. Elevated IL-6 transcription in tumor-bearing mice occured in the tumor, liver, kidney and the small intestine, and was associated with increased concentration in the circulation of bioactive IL-6 of normal size (almost-equal-to 20 000 kDa) in addition with two larger but biologically inactive serum fractions containing immune-reactive IL-6. These inactive complexes were not explained by circulating inhibitor(s). The occurrence of differently sized tumor and host-tissue IL-6 mRNAs were dependent on the subcellular location (nuclear, ribosomal, cytoplasm). the tissue type and the kind of cellular stimulation. In tumor-tissue, IL-6 was produced to the highest concentration in tumor cells, followed by inflammatory and endothelial cells respectively, but IL-6 did not seem to represent an autocrine growth factor loop as earlier reported by us for both IL-1alpha and TNFalpha in the present tumor model. In contrast, evidence supported that IL-6 acted as a paracrinic factor in this model stimulated by some other host-derived factor(s).