Multiple controls in inflammation - Extracellular and intracellular phospholipase A(2), inducible and constitutive cyclooxygenase, and inducible nitric oxide synthase

Inflammation occurs as a defensive response to invasion of the host by foreign material, often of microbial nature. This response is normally a localized protective response that at the microscopic level involves a complex series of events including dilatation of arterioles, venules, and capillaries with increased vascular Permeability, exudation of fluids including plasma proteins, and leukocyte migration into the inflammatory area. Since disease characterized by inflammation is an important cause of morbidity and mortality in humans, the processes involved in the host defense in inflammation have been and continue to be the object of several experimental studies. The role of several mediators such as histamine, serotonin, bradykinin, prostaglandins, and, more recently, cytokines and nitric oxide has been evaluated, and a contribution for each one of these mediators has been proposed. With the development of powerful molecular biology tools, it has become possible to study enzymes involved in this complex phenomenon by measuring the expression or evaluating the signaling pathways following a specific stimulus. These techniques have generated a proliferation of studies on the role of several enzymes and cytokines in inflammation. Most of these studies have been conducted in vitro on cell lines, and not many of the results have been confirmed by in vivo studies. This commentary does not pretend to analyze all of the studies and their possible incongruences, but endeavors to provoke in the reader a critical review of dogmas and current beliefs that most of the time are built on unilateral interpretation of the data. (C) 1998 Elsevier Science Inc.