Calcium metabolism and cytokines in critical illness
Abstract: Hypocalcemia is a common finding in critically ill patients, particularly in those with sepsis, and has been found to be associated with increased mortality. The pathogenesis of this altered calcium metabolism is unknown and the effects of calcium supplementation are poorly investigated. Proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), are important mediators of the inflammatory response in critical illness.In a broad mixture of patients in the emergency department (ED), elevated serum levels of IL-6 and TNF-α were associated with the severity of disease. The elevated IL-6 levels were related to an increased mortality. Also a rise in serum levels of parathyroid hormone (PTH) was common in these patients and was related to the severity of disease and increased mortality.In intensive care unit (ICU) patients, hypocalcemia and elevated serum PTH levels were common and associated to the severity of disease. Elevated levels of PTH were associated to an increased mortality. Hypocalcemia in septic patients in the ICU was not due to an increased urinary excretion of calcium or to an attenuated bone resorption, but was rather related to the inflammatory response. An increased PTHsecretion was also seen in normocalcemic ICU patients subjected to major surgery.In vitro, IL-6 was found to suppress PTH secretion by bovine parathyroid cells. In pigs, severe hypodynamic endotoxemic shock induced hypocalcemia within two hours. In these pigs calcium accumulated in ascites and in the liver. Calcium supplementation did not improve hemodynamics or survival during severe hypodynamic endotoxemic shock in pigs.In conclusion, alterations in calcium homeostasis were common in ED and ICU patients and related to a poor outcome. Hypocalcemia during sepsis was not due to urinary excretion of calcium or to an attenuated bone resorption, but rather to tissue accumulation. An interplay between inflammatory mediators and calcium metabolism was demonstrated.
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