Review: The Role of Cytokines in the Catabolic Consequences of Infection and Injury

Abstract

During infection and injury a series of metabolic events are activated that leads to a state of negative nitrogen balance and significant loss of lean body mass. This process is characterized by marked anorexia, net whole body protein breakdown, and liver anabolism. This host response initially is beneficial to the body because it helps it to fight disease and enhance healing. However, if such imbalance is maintained for long periods, it will invariably produce significant loss of lean body mass that may lead to a series of untoward clinical events. The role of the proximate cytokines, tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) as well as glucocorticoids as important mediators of many pathophysiological manifestations of infection and injury has been studied extensively. However, the involvement of other mediators, at least in skeletal muscle proteolysis during sepsis has been hypothesized, because blockade of glucocorticoids, TNF, IL-1, and IL-6 reduces but does not normalize protein breakdown rates nor does the direct application of these mediators to skeletal muscle in vitro enhance proteolysis. Furthermore other studies have suggested that the lymphokine, interferon-gamma (IFN-gamma, type II interferon or immune interferon), produces fever and enhances thermogenesis, body weight loss, and skeletal muscle depletion in rodents in a manner similar to that seen with TNF and IL-1. Cytokines appear to be major components of the host metabolic response during infection and injury. However, neither all the cytokines involved nor the exact mechanisms underlying their metabolic effects are completely understood. The regulation of muscle protein synthesis and breakdown, which largely determines the development of cachexia, appears to depend on the delicate balance between a number of regulatory substances including cytokines, glucocorticoids, catecholamines, insulin, and insulin-like growth factors.

Pentoxifylline improves insulin action limiting skeletal muscle catabolism after infection

“…First, plasma concentrations of TNF are increased after infection (Chang & Bistrian 1998). Secondly, TNF blocks the action of insulin through its ability to inhibit insulin receptor tyrosine kinase activity (Feinstein et al 1993, Kroder et al 1996, Peraldi et al 1996, Peraldi & Spiegelman 1998.…”

Superpulsed laser therapy on healing process after tooth extraction in patients waiting for liver transplantation

“…2) At the laser treatment sites, the increase of IL-6 was also accompanied by the increase in IL-10, a cytokine possessing anti-inflammatory activity [39]. Therefore, IL-10 can counterbalance the proinflammatory properties of IL-6, favouring the healing process.…”

“…Twenty-five microliters of a PCR mixture containing cDNA template equivalent 40 ng of total RNA, 5 pmoles each of forward and reverse primers, and 2 IQ SYBR Green SuperMix (Bio-Rad, Hercules, CA) were amplified using an iCycler PCR instrument (Bio-Rad, Hercules, CA) with an initial melt at 95°C for 10 min, followed by [35][36][37][38][39][40] cycles at 95°C for 40 s, annealing temperature for each primer set for 40 s, and 72°C for 40 s. A final extension of 7 min at 72°C was applied. Each sample was tested in duplicate, and threshold cycle (Ct) values were averaged from each reaction.…”

Inflammation and Immunopathogenesis of Tuberculosis Progression

“…All three cytokines may cause severe pathology. They have been implicated in microvascular thrombosis, capillary leak and neutrophilic chemotaxis, produce organ dysfunction, systemic inflammation, acute-phase response, cachexia and fever (Tracey et al, 1987;Hernandez-Pando et al, 1994;Chang & Bistrian, 1998;Bekker et al, 2000;Agriles et al, 2005;Oliveira et al, 2008).…”