Cogence Clinical Pearl

What the research says…

Muscles make IL-6. IL-6 crosses the blood brain barrier and promotes vasopressin release from the pituitary. Vasopressin reduces urine formation, changing the sodium concentration in the blood. The osmotic changes that result can drive a dangerous and sometimes fatal cerebral edema.

Application…

In athletes, the culture of hydration in preparation for endurance events and during triathlons and other endurance sport activities risks triggering Exercise Associated Hyponatremia (EAH), which can be fatal. Athletes should use electrolyte repletion as part of their hydration strategy and have blood electrolyte levels monitored post-event, to provide appropriate surveillance that informs decisions about electrolyte management.

If a patient doing endurance sports develops EAH, they may become delerious, vomit, lose consciousness, etc. If the patient is transported to the hospital, labs will include creatine kinase (CK, also known as creatine phosphokinase, CPK). The level will be very high, because of muscle breakdown due to the intense, prolonged sports activity. Because of a very high CK level, the risk is that the patient will be mis-diagnosed as having rhabdomyolysis. The treatment for rhabdomyolysis is hydration. If the patient is given IV hydration, it could kill them. What they need is an IV with a bolus of sodium, followed by proper management to get the sodium level up. The key here is to monitor the sodium, both initially and ongoing, to be sure you’re accomplishing restoration of normal sodium levels.

In the outpatient population, persistence of IL-6 mediated inflammation can also drive changes in sodium level that can likewise drive cerebral edema. Frequent surveillance of electrolyte levels in chronically inflamed patients can help identify problems that can contribute to a worsening of cognitive function and acceleration of brain-based disease.

Beneficial health effects of exercise–the role of IL-6 as a myokine.

Trends Pharmacol Sci. 2007 Apr;28(4):152-6.

Pedersen BK, Fischer CP.

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Abstract

It is not clear how contracting skeletal muscles mediate the numerous and diverse metabolic and physiological effects that are beneficial for health. Researchers have searched for a muscle-contraction-induced factor – an ‘exercise factor’ – that mediates some of the exercise effects in other tissues such as the liver and adipose tissue. In our search for such a factor, we encountered the cytokine interleukin (IL)-6, which is produced by contracting muscles and released into the blood. We propose that muscle-derived IL-6 meets the criteria of an exercise factor and that such classes of cytokine should be named ‘myokines’. The discovery of contracting muscle as a cytokine-producing organ creates a new paradigm: skeletal muscle as an endocrine organ. By contracting, it stimulates the production and release of myokines that can influence metabolism in tissue and organs. Newly identified myokines and their receptors could serve as targets in the treatment of metabolic disorders and other diseases.

Hyponatremia and inflammation: the emerging role of interleukin-6 in osmoregulation.

Nephron Physiol. 2011;118(2):45-51.

Swart RM, Hoorn EJ, Betjes MG, Zietse R.

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Abstract

Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided.

Exercise-associated hyponatremia: role of cytokines.

Am J Med. 2006 Jul;119(7 Suppl 1):S74-8.

Siegel AJ.

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Abstract

Exercise-associated hyponatremia (EAH) has emerged in recent years as a life-threatening complication of endurance sports that may lead to fatal cerebral and pulmonary edema. Defined as a serum sodium concentration <135 mEq/L (1 mEq/L = 1 mmol/L), symptomatic EAH is a dilutional hyponatremia with abnormal fluid retention mediated by decreased urine production, which is a variant of the syndrome of inappropriate antidiuretic hormone secretion. Strategies for prevention and treatment must take into account the pathophysiology underlying this dominant clinical paradigm. Beyond educating runners to drink moderately, monitoring changes in body weight during endurance sports may facilitate the early detection of positive fluid balance characteristic of symptomatic cases. Rapid diagnosis by point-of-care testing indicates the need for fluid restriction in mild cases and emergent treatment with hypertonic (3%) NaCl to reverse acute hypotonic encephalopathy. The efficacy of arginine vasopressin V(2) receptor antagonists warrants study as an alternative treatment to loop diuretics for volume overload in these patients. Nonosmotic stimulation of arginine vasopressin secretion may be mediated in part by enhanced release of muscle-derived interleukin-6 during glycogen depletion, linking exertional rhabdomyolysis to the pathogenesis of EAH.