Interleukin‐15 does not attenuate TNF‐alpha and/or aging induced pro‐apoptotic signaling in skeletal muscles

Abstract

In this study, we tested the hypothesis that IL-15 would attenuate apoptosis induced by TNF-alpha in vitro and/or aging in vivo, specifically in skeletal muscles. Treatment of C2C12 myoblasts with 20ng.ml-1 of TNF-alpha decreased cell viability and reduced mitochondrial integrity. However, treatment with 20ng.ml-1 of IL-15 did not attenuate the TNF-alpha induced decrease in cell viability and mitochondrial integrity, indicating IL-15 failed to protect against TNF-alpha induced apoptosis in vitro. To test the effects of IL-15 on muscle in vivo, IL-15 (100ìg.kg-1 per day) was administered via osmotic pumps, to young adult (n=6) and aged (n=6) Fischer344 x Brown Norway (FBN) rodents for 14d. DNA fragmentation was greater in plantaris, soleus, and medial gastrocnemius muscles from aged animals and in all muscles from IL-15 treated animals compared to muscles from control animals. IL-15 had minimal effects on the incidence of DNA fragmentation in left ventricle, liver, or spleen of experimental rodents. These data do not support our initial hypothesis and suggest that IL-15 does not prevent apoptotic signaling in induced by TNF-alpha and in muscle tissue from aged rodents. The proposed anti-apoptotic property of IL-15 may be tissue specific and/or specific to the degree of pathology; however, additional research is required to more clearly decipher this role. Supported by: R01 AG-021530 (Alway), RFG-14 (Pistilli)