Range Of Mediators Research Articles

Mediator removal with CRRT: Complement and cytokines

The evidence from animal sepsis models that hemofiltration may ameliorate the hemodynamic changes that occur in septic shock has led to speculation that continuous renal replacement therapy may have nonrenal benefits in septic patients. Much of the subsequent work has been done to elucidate the mechanisms of this benefit, in particular the role of removal of inflammatory mediators including cytokines and complement. The significance of extracorporeal removal of such products is dependent on the relative importance of endogenous production and clearance in the setting of sepsis and multiple organ failure and on the method of blood purification. This article reviews the evidence thus far, consisting of in vitro, animal, and human studies; a range of mediators (TNFα, IL-1β, IL-6, IL-8, complement factors C 3a, C 5a, and D); various membranes (polyacrylonitrile, polysulfone, and polyamide); and clearance by diffusion, convection, and adsorption. The most consistent results suggest that the plasma levels of some mediators are lowered by a combination of membrane adsorption and convection, the clinical significance of which is still uncertain. The review shows the need for further work to unravel the role of CRRT in treating septic patients.

Bronchial Epithelial Cells

The bronchial epithelium has metabolic and immunological properties that involve the release of a range of mediators and interaction with other cell types within the lung. It also acts as a dynamic barrier, regulating the penetration and the traffic of a number of molecules between the body and the environment. Many of these functions seem to be altered during the airway inflammation associated with bronchial asthma. In asthma the epithelium is often shed, and the extent of denudated basement membrane significantly correlates with bronchial hyperreactivity. Moreover, bronchial epithelial cells from patients with asthma are in an activated state. They release inflammatory mediators such as arachidonic acid metabolites and cytokines, and express surface markers such as adhesion molecules and major histocompatibility complex antigens. The functional activation of these cells seems to be correlated with the clinical severity of asthma. Great attention has recently been focused on the effect of drugs on the phenotypical and functional alterations of bronchial epithelial cells in asthma. Several drugs, particularly corticosteroids, can promote the repair of the desquamated areas of the bronchi and decrease the release of inflammatory mediators such as endothelin, interleukin-8 and granulocyte-macrophage colony-stimulating factor. Taken together, this evidence indicates that bronchial epithelial cells play a pivotal role in the pathophysiology of asthma and represent an important target for future therapeutic approaches.