Mediators Of Acute Inflammation Flashcards
List the most important mediators of inflammation
1) Vasoactive amines (histamine and serotonin)
2) Lipid products ( prostaglandins and leukotrienes)
3) Cytokines including chemokines
4) products of complement system
Mediators are either secreted by ________ or mediated by________
Cells or mediated by plasma proteins
Histamine source and action
Source: mast cells, basophils, or platelets
Action: Vasodilation of arterioles, increased vascular permeability and endothelial activation
Prostaglandins source and action
Source: mast cells, leukocytes
Action: vasodilation, fever and pain
Leukotrienes source and action
Source: mast cells, leukocytes
Action: increased vascular permeability, chemokines, leukocytes adhesion and activation
C-3a and C5b what do they do
Parts of the complement system that trigger release of mast cell granules hence histamine
List other things that can trigger the release of histamine asides C3a and C5b
Substance p and cytokines like IL-1 and IL-8
What mediates the vasoactive effect of histamine
HI receptors on microvascular endothelial cells
Serotonin location and action
Location: platelets and some neuro endocrine cells like the GI tracts, also in mast cells of rodents but not humans
Action: Functions primarily as a neurotransmitter in the GI tract
A vasoconstrictor
What type of receptors do arachidonic acid metabolites bind to
G- protein coupled receptors on many cell types and mediate virtually every step in inflammation
Arachidonic acid metabolites that cause vasodilation
Prostaglandin I2, D2,E2 E1
Arachidonic acid metabolites that cause vasoconstriction
Thromboxane A2, leukotrienes C4,D4, E4
Arachidonic acid metabolites that cause increased vascular permeability
Leukotrienes C4, D4, E4
Arachidonic acid metabolites that cause chemo taxis and leukocyte adhesion
Leukotrienes B4, HETE
Prostaglandins are produced by
Mast cells, macrophages, endothelial cells and many other cell types
TxA2 is a potent _____________
Platelet aggregating agent and vasoconstriction
It is unstable and rapidly converted to its inactive state Tx B2
Prostacyclin is a potent __________
Inhibitor of platelet aggregation and a vasodilator
A thromboxane prostacyclin imbalance is seen where
Thrombus formation in coronary and cerebral blood vessels
What is the predominant lipoxygenase in neutrophils
5- lipoxygenase
Functions of leukotrienes
Intense vasoconstriction, bronchospasm( asthma) and increased permeability of venules
Lipoxins functions
Suppress inflammation by inhibiting recruitment of leukocytes
They inhibit neutrophil chemotaxis and adhesion to endothelium
Cyclooxygenase inhibitors
Aspirin, NSAIDS like ibruprofen
Cox 2 inhibitors may increase the risk of
Cardiovascular and cerebrovascular events
Inhibitors of leukotrienes
Zileuton used for asthma treatment
What are corticosteroids used for
Anti inflammatory agents that reduce transcription of genes encoding COx 2, phospholipids A2, pro inflammatory cytokines
What is responsible for systemic acute phase response
IL-1, TNF, IL-6
List systemic acute phase responses
Fever
Sepsis
Sustained production of TNG contributes to cachexia thay accompanies some chronic infections
TNF antagonists are effective in treatment of
Chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, some inflammatory bowel disease
Complications of TNF antagonist
Patients become more susceptible to mycobacteria’s infection
Example of CXC chemokines
IL-8
Example of C-C chemokines
MCP-1 ( monocyte chemoattractant proteins), MIP-1alpha ( macrophages inflammatory protein), Eotaxin, RANTES
Example of C chemokines
Lymphotactin
Chemokines can be classified into four major groups list
1) CXC chemokines e.g IL-8
2) C-C chemokines e.g MCP-1, MIP-1, eotaxin, RANTES
3) C chemokines lymphotactin
4) CX3C chemokines e.g fractalkine
Example of CX3C chemokines
Fractalkine
Functions of chemokines in acute inflammation
1) stimulates neutrophil attachment to the endothelium by increasing integrin affinity
2) stimulates chemotaxsis
3) maintenance of tissue architecture
Functions of compliment system
1) inflammation
2) opsonisation and phagocytosis
3) Cell lysis
