Horst Ibelgaufts' COPE: Cytokines & Cells Online Pathfinder Encyclopaedia COPE needs your support to remain a free service!

inflammation

A general name for reactions occurring after most kinds of tissue injuries or infections or immunologic stimulation as a defense against foreign or altered endogenous substances. Inflammatory reactions involve a number of biochemical and cellular alterations the extent of which correlates with the extent of the initial trauma (see also: wound healing). Inappropriate activation of inflammatory responses is the underlying cause of many common diseases and inflammatory reaction are, therefore, also an important target for drug development.

The most prominent systemic manifestation of inflammation is an elevation of body temperature and a variety of biochemical alterations known as the acute phase reaction which leads to the synthesis of acute phase proteins in the liver.

The local inflammatory reaction is characterized by an initial increase in blood flow to the site of injury, enhanced vascular permeability, and the ordered and directional influx and selective accumulation of different effector cells from the peripheral blood at the site of injury. Influx of antigen non-specific but highly destructive cells (neutrophils) is one of the earliest stages of the inflammatory response. These cells mount a rapid, non-specific phagocytic response.

At a later stage monocytes, macrophages, and cells of other lineages of lymphocytes (specific subsets of T-cells and B-cells) appear at the site of injury. These cell types are associated with antigen-specific and more tightly regulated immune responses and once activated also produce protective and inflammatory molecules. An exudation of plasma into the lesion in the early stage is observed also.

Inflammatory cells express increasing numbers of cell-surface proteins and glycoproteins known as cell adhesion molecules. Endothelial cells are also activated during the initial phase of the inflammatory response and then express, among other things, adhesion molecule counterreceptors. The regulated expression of these molecules allows for the precise trafficking of circulating leukocytes to inflammatory sites. Cellular attachment of immune cells to endothelial cells lining blood vessels surrounding the inflammatory site prevents them from being swept past the site of infection or tissue damage and is a crucial step required for the subsequent emigration of these cells into the surrounding inflammatory tissues (extravasation) (see also: Motogenic cytokines).

The highly efficient process of cellular influx to inflammatory sites is mediated by a plethora of mediator substances supporting and dispersing inflammation. These mediators are found in the serum or tissue fluids, are released by degranulating cells, and are secreted also by inflammatory cells upon activation, or activated endothelial cells in blood vessels at the site of inflammation. They serve as muscle-active and edema-promoting substances, chemotaxins (see: Chemokines; see also: Chemotaxis), and cellular activators and inducers of all kinds of effector cells engaged in the inflammatory response.

Inflammatory mediators include some well studied compounds such as anaphylatoxins of the complement cascade, kinins of the coagulation system, leukotriens, prostaglandins, and many other lipid mediators. Another group of mediators are neuropeptides such as Tachykinins, VIP (vasoactive intestinal peptide), and VPF (vascular permeability factor). These substances enhance capillary permeability and have vasodilatatory and bronchoconstrictory activity and also increase the production of mucus.

A number of cytokines, known collectively as pro-inflammatory cytokines because they accelerate inflammation, also regulate inflammatory reactions either directly or by their ability to induce the synthesis of cellular adhesion molecules or other cytokines in certain cell types. The major pro-inflammatory cytokines that are responsible for early responses are IL1-alpha, IL1-beta, IL6, and TNF-alpha. Other pro-inflammatory mediators include LIF, IFN-gamma, OSM, CNTF, TGF-beta, GM-CSF, IL11, IL12, IL17, IL18, IL8 and a variety of other chemokines that chemoattract inflammatory cells, and various neuromodulatory factors (see: Neuroimmune network). The net effect of an inflammatory response is determined by the balance between pro-inflammatory cytokines and anti-inflammatory cytokines (for example IL4, IL10, and IL13, IL16, IFN-alpha, TGF-beta, IL1ra, G-CSF, soluble receptors for TNF or IL6). Activation of IL1-beta by various caspases proceeds in a large multiprotein complex that has been termed inflammasome.

The observed redundancy among the different cytokines and other mediators of inflammation generally guarantees a substitution or complementation of individual components that may have been inactivated under pathological conditions.

Under normal circumstances these cascades of inflammatory reactions induced by the mediators are strictly regulated. Failure to do so can lead to multiple organ failure (see also: Systemic inflammatory response syndrome). Inflammatory mediators and suitable inhibitors are, therefore, of key interest for modulating and ameliorating the effects of inflammatory reactions and their sequelae.

LAST MODIFIED: January 2002

See REFERENCES for entry inflammation

COPE Homepage

Top of Page

 

#

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

Q

R

S

T

U

V

W

X

Y

Z

Space for your TEXTLINK ADVERTISEMENTS. Please Inquire

---

---

supports the COPE bioinformatics project with an unrestricted educational grant
Inquiries from other sides welcome

---

Created, developed, and maintained by Prof Dr H Ibelgaufts               About the author of COPE   |    Contact COPE   |    postcard and stampware

---

Access to COPE is free only for academic institutions and non-profit organizations. OTHER USERS: must contact COPE and pay a site licence fee. Non-payment of the site licence fee is a serious breach of COPE's binding Usage Agreement. If you do not wish to be bound by this agreement, do not use COPE

COPE is not in the public domain! The commercial use of COPE contents is not allowed. Download of complete offline-readable copies and the use of automatic extraction methods are prohibited! Usage Agreement, Disclaimer, Copyright Notice   |  All rights reserved by H Ibelgaufts   |  Privacy Statement U L T R A   P O S S E   N E M O   O B L I G A T U R

cope.cgi version 24.7.07, revision Jun 14, 2010. (c) JI. Powered by Perl 5.008008 [b=5]