CYTOKINES AND METABOLIC DYSFUNCTION AFTER SEVERE HEAD-INJURY

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect orga n function, cause a systemic response to injury, and may cause seconda ry tissue injury. The metabolites involved in this cascade are numerou s and complex. Cytokines are important cell-to-cell communication medi ators during injury. It is speculated that cytokines, such as interleu kin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and i nterleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular casca de of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutro philia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, incre ased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokin es have also been implicated in organ failure. Infusion of cytokines i n basic science trials revealed that organ functions of the gut, liver , and lung are negatively altered by high-dose cytokine infusion. Infu sion of certain cytokines has been shown to cause death of brain cells , increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by de creasing serum cytokine activity. We hypothesize that cytokines that a re elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.