TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-ALPHA PRODUCTION IN CACHECTIC, TUMOR-BEARING MICE

Weight‐stable mice bearing a syngeneic, methylcholanthrene‐induced, rapidly growing tumor lost approximately 22% of their lean tissue, became significantly hypoalbuminemic and had a marked increase in serum amyloid P concentrations during progressive tumor growth. Tumors from cachectic mice were producing both TNF‐α and IL‐1α in vivo as documented by the presence of TNF‐α and IL‐1α mRNA and immune‐reactive protein for IL‐1α. Only spleens from tumor‐bearing mice had statistically significantly elevated quantities of IL‐1 mRNA. In general, alterations in tissue concentrations of IL‐1 mRNA in tumor‐bearing animals agreed qualitatively with those found in endotoxin‐stimulated, nontumor‐bearing control mice. However, endotoxin‐stimulated mice had significantly elevated tissue concentrations of TNF mRNA in spleen and livers, while TNF mRNA levels were not significantly increased in any host tissues. Cytokine mRNA levels in tumor tissue were not higher than those found constitutively in various tissues from non‐tumor‐bearing control animals. Plasma from tumor‐bearing mice and endotoxinstimulated controls contained high levels of IL‐6 but low (endotoxin‐stim.) or no measurable levels (tumor‐bearing) of either IL‐1 or TNF. When tumor cells from cachectic mice were placed into long‐term cell culture, immune reactive TNF‐α and IL‐1α were produced, but IL‐6 bioactivity was not produced in measurable amounts. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company