Hyperthermia increases interleukin-6 in mouse skeletal muscle

Abstract

Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-α gene expression was routinely suppressed at all levels of hyperthermia (40.5-42°C) in the isolated models, but TNF-α was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a "heat stress sensor" at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6.

Acute heat stress activated inflammatory signaling in porcine oxidative skeletal muscle

“…2010), and in muscle NF‐ κ B signaling did not appear to contribute to dysfunction in heat stroke models (Welc et al. 2012, 2013b). …”

“…In several studies modeling heat stroke IL‐6 has been shown to be increased and cytoprotective (Leon 2007; Welc et al. 2012, 2013b; Phillips et al. 2015).…”

“…In particular, interleukin‐6 (IL‐6) is strongly induced in muscle during heat stroke and appears to be cytoprotective for a number of organ systems (Welc et al. 2012), however, it is blunted during 12 h of hyperthermic exposure (Ganesan et al. 2016).…”

Increasing heat storage by wearing extra clothing during upper body exercise up-regulates heat shock protein 70 but does not modify the cytokine response

“…Given the importance of temperature elevations in this response (Welc et al, 2012), this exercise modality may particularly benefit from interventions increasing heat stress, because in contrast to lower body exercise, upper body exercise generates less metabolic heat and as such the increases in T core for the same relative exercise intensity are lower for this modality (Gass & Gass, 1998). Lower body exercise comparable in relative intensity and duration as the present study induces two to three times the increase in T core when performed in cool or thermo-neutral conditions (Gibson et al, 2014;Niess et al, 2003;.…”

Fire service instructor's undergarment choice to reduce Interleukin-6 and minimise physiological and perceptual strain

“…Furthermore, all participants displayed similar trends, suggesting that WBL may cause a reduced inflammatory response compared to the other conditions. Previous studies have noted increases in IL-6 due to heat exposure or exercise (Scharhag et al 2005;Welc et al 2012). Firefighters have also demonstrated increases in IL-6 following 40 min of simulated fire and rescue tasks in the heat (Walker et al 2015).…”