Deletion of the gene encoding MyD88 protects from anorexia in a mouse tumor model
2010 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 24, no 4, 554-557 p.Article in journal (Refereed) Published
The anorexia-cachexia syndrome, characterized by a rise in energy expenditure and loss of body weight that paradoxically are associated with loss of appetite and decreased food intake, contributes significantly to the morbidity and mortality in cancer. While the pathophysiology of cancer anorexia-cachexia is poorly understood, evidence indicates that pro-inflammatory cytokines are key mediators of this response. Although inflammation hence is recognized as an important component of cancer anorexia-cachexia, the molecular pathways involved are largely unknown. We addressed this issue in mice carrying a deletion of the gene encoding MyD88, the key intracellular adaptor molecule in Toll-like and interleukin-1 family receptor signaling. Wild-type and MyD88-deficient mice were transplanted subcutaneously with a syngenic methylcholanthrene-induced tumor (MCG 101) and daily food intake and body weight were recorded. Wild-type mice showed progressively reduced food intake from about 5 days after tumor transplantation and displayed a slight body weight loss after 10 days when the experiment was terminated. In contrast, MyD88-deficient mice did not develop anorexia, and displayed a positive body weight development during the observation period. While the MyD88-deficient mice on average developed somewhat smaller tumors than wild-type mice, this did not explain the absence of anorexia, because anorexia was seen in wild-type mice with similar tumor mass as non-anorexic knock-out mice. These data suggest that MyD88-dependent mechanisms are involved in the metabolic derangement during cancer anorexia-cachexia and that innate immune signaling is important for the development of this syndrome.
Place, publisher, year, edition, pages
Amsterdam: Elsevier Science B.V. , 2010. Vol. 24, no 4, 554-557 p.
Anorexia, Cachexia, Cancer, MyD88, Mice, Innate immunity
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-56458DOI: 10.1016/j.bbi.2010.01.006ISI: 000277206600006OAI: oai:DiVA.org:liu-56458DiVA: diva2:319252