The human inflammatory response.
Inflammation is a protective response of vascularized tissue normally elicited toward nonself-determinants or tissue injury. Inflammation functions as part of normal host surveillance mechanisms to destroy or quarantine both harmful agents and damaged tissue. Most forms of inflammation are exaggerated out of proportion to the stimulus, because humoral amplification systems recruit additional components of the immune system initiating the production of proinflammatory mediators, including cytokines synthesized by activated macrophages. These act as secondary messengers to induce synthesis and expression of specific adhesion molecules on endothelial cells and white cells. Polymorphonuclear leukocytes play a central role in the acute inflammatory response. Anaphylaxis, an immediate hypersensitivity reaction to substances administered in the perioperative period, serves as a useful model for some of the problems of acute inflammation because there are important interrelationships with the cardiovascular system, endothelium, and coagulation. Mast cells and basophils produce the acute inflammation associated with anaphylaxis mediated by immunoglobulin E (IgE) antibodies, whereas the immunoglobulin G (IgG)-antigen interaction activates the complement cascade to generate anaphylatoxins, specifically C5a. Activation of white cells causes release of proteolytic enzymes, production of oxygen-derived free radicals, and the synthesis of a variety of lipid mediators. Protamine sulfate is one of the most common causes of life-threatening anaphylactic reactions during cardiac surgery. Differing responses occur, dependent on the presence of either IgE or IgG antibodies with the activation of the mast cell or the complement system, respectively. The many different amplifying pathways that can be recruited during anaphylaxis and the array of mediators involved are important when therapeutic intervention is considered. The challenge for the future will be to identify a pharmacologic agent that will arrest the inflammatory cascade and thus prevent further amplification and resultant host injury.
Levy
J H
JH
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology