Sepsis-related alterations in non-immune cell-signaling

Traditionally, sepsis is defined as a systemic inflammatory reaction of the organism to Gram-negative bacterial leading to septic shock--characterized by hemodynamic derangements--and eventually to septic multi-organ malfunction. Sepsis syndrome is diagnosed when fever and other abnormalities of vital signs are present along with abnormalities of one or more organ systems that are not the site of infection and trauma (but with an identifiable locus of infection), and is associated with a range of 30% to 50% mortality. In the United States, one of the most frequent and serious problems confronting clinicians is the management of a serious infection and the systemic response to the infection, such as sepsis. Endotoxins are responsible for initiation of septic shock, which increases the number of fatalities in Gram-negative bacteremia among patients. Inflammation is meant to preserve health, but it is a double-edged sword because of its potential to cause irreversible tissue damage. Like other physiologic systems, the inflammatory response must be turned on and off as required. At present, our knowledge of the pathophysiologic changes at the initiation of the inflammatory process is in infancy, and the mechanism(s) of these signals are relatively less understood. Sepsis gives rise to pronounced metabolic alterations in various organs and tissues, particularly with increased muscle protein breakdown and stimulated hepatic protein synthesis. Although it leads to muscle wasting and increased nitrogen secretion, protein metabolic alteration also serves as an adaptive response in early sepsis as it provides amino acids for hepatic acute phase protein synthesis and gluconeogenesis. Calcium plays vital roles in the intracellular regulation of a variety of cellular responses (for example, contraction, secretion, cell-cell communication, cell proliferation) under physiologic conditions in various cell-types. Alterations in intracellular Ca2+ regulation leading to elevated cytosolic Ca2+ concentration could not only interfere with the cellular responses but also activate lytic enzymes such as proteinases and phospholipases. The objective of this article is to discuss the experimental findings that indicates relationship between alterations in cellular signaling and protein metabolic derangements in non-immune cells (skeletal muscle or liver) during sepsis and inflammation.