IL6 Signaling during Cancer Cachexia Progression: The Female Response Academic Article uri icon

abstract

  • Cachexia arises secondary to many chronic diseases and accounts for about 30% of cancerrelated deaths. Cachexia occurs in both sexes, but its etiology and progression have been almost exclusively examined in the male. Interleukin6 (IL6) has become an attractive therapeutic target as IL6 signaling is a recognized regulator of male ApcMin/+ mouse cancer cachexia progression. Despite established sexdependent inflammatory responses, how IL6 signaling contributes to female cancer cachexia progression is unknown. Consequently, we examined the role of circulating IL6 for female ApcMin/+ mouse cancer cachexia progression. Female ApcMin/+ mice weight and functional testing were monitored until sacrifice at 18 weeks of age. A second group of female ApcMin/+ mice underwent IL6 overexpression at 15 weeks of age. Blood and hindlimb muscle were collected to examine IL6 levels and downstream signaling. Mice were stratified into weight stable, initially cachectic, and severely cachectic groups. Plasma IL6 did not differ between groups (17.6 6.7; 34.4 18.9; 39.3 13.1 pg/ml); however, muscle IL6 mRNA correlated with body weight loss and hindlimb muscle mass (p=0.008, 0.019). Muscle IL6r, gp130, and SOCS3 mRNA expression did not change with cachexia severity. Muscle STAT3 phosphorylation increased with severe cachexia compared to initial cachexia (14.8 1.6 vs 5.2 2.1 fold change relative to WT levels). Surprisingly, IL6 overexpression did not increase muscle IL6 signaling or bodyweight loss. Overall, elevated IL6 does not exacerbate cachexia progression in the female ApcMin/+ mouse.

published proceedings

  • The FASEB Journal

author list (cited authors)

  • Hetzler, K., Hardee, J., Puppa, M., Narsale, A., Sato, S., Davis, J., & Carson, J.

complete list of authors

  • Hetzler, Kimbell||Hardee, J||Puppa, M||Narsale, A||Sato, S||Davis, J||Carson, J

publisher