The crucial role of systemic responses in the innate (non-adaptive) host defense

We suggest that successful defense against microbial invasion requires both local inflammation and systemic anti-inflammation. The key systemic respon ses involve the hypothalamic-pituitary-adrenocortical axis. the sympathetic -adreno medullary axis, acute phase protein production, thermoregulation an d alterations in leukocyte responsiveness to agonists such as bacterial end otoxin. These integrated responses raise blood and tissue concentrations of several anti-infective molecules, mobilize leukocytes into the circulation , and increase blood flow to injured or infected sites. They also neutraliz e cytokines, proteases and oxidants that enter the bloodstream from inflame d local sites and forestall endothelial activation in distant vessels. Toge ther, these forces help concentrate activated phagocytes at injured or infe cted local sites while preventing potentially damaging inflammation in unin volved tissues.