Interleukin‐4 is a Potential Regulator of Satellite Cell Function in Response to Acute Myotrauma in Humans

Interleukin‐4 (IL‐4) has been implicated in myoblast fusion and growth; however, the localization of IL‐4 to satellite cells (SC) in humans, has not been demonstrated. Furthermore, the role of IL‐4 in SC in response to acute injury in humans has not been investigated. Eight subjects (age 22 ± 1 y; 79 ± 8 kg) performed 300 maximal unilateral leg lengthening contractions (3.14 rad.s−1) and muscle samples were collected at PRE, 4 (T4), 24 (T24), 72 (T72), and 120 hr (T120) post intervention. Immunohistochemical analysis revealed that IL‐4 protein was localized with Pax7+ SC at T4, T24 and at T72, with no visible IL‐4 detected at PRE. IL‐4 and IL‐4R mRNA demonstrated significant (p < 0.05) 4.4 fold upregulations at T4 while IL‐4R maintained this high expression at T24 post exercise (p < 0.05). Similarly, a downstream target of IL‐4, SOCS1, demonstrated a 2.9 fold increase (p < 0.05) at T4. Furthermore, IL‐13 mRNA levels remained low until T120 where it became significantly increased compared with all other time points (p < 0.05). Pearson product correlation analysis demonstrated positive associations between IL‐4, IL‐4R (p < 0.001, R2 = 0.67) and SOCS1 (p < 0.001, R2 = 0.69) mRNA expression levels. Furthermore, IL‐4R mRNA correlated with SOCS1 expression (p < 0.001, R2 = 0.57). These data suggest a role for IL‐4 in the SC response to acute myotrauma in humans, possibly signalling via the STAT6 pathway.