Cancer cachexia is mediated in part by the induction of IL-6-like cytokines from the spleen.
The development of cancer cachexia has been linked to cytokines related to interleukin6 (IL-6). We examined the kinetics of IL-6, IL-11, oncostatinM (OSM) and leukaemia inhibitory factor (LIF) induction in the splenocytes of tumour-bearing mice. Using a lung carcinoma line, which grows in C57BL/6J mice, we observed that when the tumour grew and cachexia was observed, the splenocytes produced IL-6, IL-11, and OSM, but not LIF. Cytokine expression was observed within 1 week (day 3 for IL-6 and IL-11, and day 1 for OSM) of administration of tumour cells, and was observed in splenocytes without tumour metastases to the spleen. Cytokine expression preceded cachexia (determined by changes in serum triglyceride levels and decrease in epididymal fat-pad weights) development by over 1 week. Exogenous administration of IL-11 resulted in the accelerated onset of cachexia, compared to control protein treatment, but without an effect on the tumour burden. In vivo treatment with a neutralizing dose of anti-OSM antibody inhibited the triglyceride dysregulation only until the synthesis of IL-6 and IL-11 began in the spleen (day 3). Afterward, IL-6 and IL-11 induced lipid catabolism in the absence of functional OSM. We conclude from the data described above that cachexia developed due to a systemic cytokine response induced by a tumour burden, and that IL-6-like cytokines contributed independently to lipid hypercatabolism in the aetiology of cancer cachexia.
Barton
B E
BE
Department of Surgery, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, MSB G-519, 185 S. Orange Avenue, Newark, NJ 07103, USA. bartonbe@umdnj.edu
Murphy
T F
TF
D000818:Animals; D015153:Blotting, Western; D002100:Cachexia / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000378:metabolism; D017370:Interleukin-11 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000150:complications*; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; C508352:Osm protein, mouse; D010455:Peptides; D011994:Recombinant Proteins; D053683:Oncostatin M