Senescent Skeletal Muscle Produces a Distinct Cytokine Secretory Profile in Response to Endotoxin Exposure in Vitro

Skeletal muscles are thought to contribute to both pathogen detection and cytokine secretion as a part of the innate immune response. Skeletal muscle fibers contain toll like receptors (TLRs) that bind a wide array of bacterial, viral, and fungal ligands, inducing signal transduction and subsequent cytokine production. Aging populations have significantly greater mortality annually from influenza, incidence of bacterial and fungal infections, and diminished vaccine efficacy. In senescent mice, macrophage TLR expression and cytokine secretion are known to decline in some tissues. It is unknown if skeletal muscle also exhibits age associated changes in innate immune contribution. The objective of this experiment was to determine if there are alterations in cytokine secretory response of aged skeletal muscle to lipopolysaccharide (LPS), a potent TLR2 and TLR4 ligand. Matched solei muscles from 12–15‐week‐old male C57BL/6 mice (n=8; “young”) and 16‐month‐old (n=10; “old”) were excised in oxygenated (95%O2/5%CO2) Krebs solution and placed under 1 g of tension in 2 ml baths at 35°C. After a 30‐min acclimation period (T0), the buffer was changed and muscles were exposed to 1 μg/ml LPS. Bath samples at T0, 1 hr (T1) and 2 hr (T2) were taken, combined with a protease inhibitor cocktail and frozen at −80°C prior to Luminex multiplex analysis. In conclusion, solei from old mice generally displayed a diminished cytokine secretory response, with particularly large decrements in IL‐12p70, IL‐6, MCP‐1, KC, and G‐CSF compared to young controls (see Table 1). Interestingly, solei from old mice displayed relatively large increases in IL‐1α, with smaller, yet also significant increases in IL‐10 and TNFα. The drastically lowered IL‐6 secretion in older mice may diminish the normal inhibition on IL‐1α and subsequent TNFα production. The small rise in IL‐10 in the elder mice may serve as a compensatory mechanism to lower IL‐1α due to diminished IL‐6 response. It may also contribute towards the severely lowered KC production, as is seen with the inhibition of human KC homologue IL‐8 by elevated IL‐10. The combination of radically lower IL‐6 and KC secretion, and increased IL‐1α and TNFα may produce an environment favoring excessive inflammatory, yet reduced chemotactic responses to pathogen exposure in older mice. Support or Funding Information Supported by NIGMS R01GM118895‐01 and the BK and Betty Stevens Endowment. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .