Inflammation and Anti-inflammatory

What are the main functions of inflammation?

Mobilises defensive cells; limits spread of pathogens; kills pathogens; initiates tissue repair

What occurs in phase 1 of acute inflammation?

Exudation of plasma fluid containing inflammatory mediators

What cells dominate phase 2 of acute inflammation?

Neutrophils

What happens in phase 3 of acute inflammation?

Monocytes enter tissue and differentiate into macrophages

How are inflammatory products cleared from tissues?

Through the lymphatic system

What are the 5 cardinal signs of inflammation?

Heat; redness; swelling; pain; loss of function

What causes heat and redness during inflammation?

Vasodilation increasing blood flow

What causes swelling during inflammation?

Protein leakage into ECF causing water movement by osmosis

What causes pain during inflammation?

Release of prostaglandins and histamine activating neurons

What is leukocyte extravasation?

Movement of leukocytes out of blood vessels into tissues

What is chemotaxis?

Attraction of leukocytes to a site of damage

What can chronic inflammation eventually lead to?

Fibrosis/scarring of tissue

What is the main precursor of prostaglandins and leukotrienes?

Arachidonic acid

What enzyme releases arachidonic acid from membrane phospholipids?

Phospholipase A2

What is the role of cyclooxygenase (COX)?

Converts arachidonic acid into prostaglandins and thromboxanes

What increases COX expression?

Inflammatory signals

What are the main effects of prostaglandins?

Vasodilation; pain; fever

What does PGD2 do?

Vasodilation and inhibition of platelet aggregation

What does PGE2 do?

Acts as the main inflammatory prostaglandin

What does PGI2 do?

Vasodilation and inhibition of platelet aggregation

What does PGF2α do?

Bronchoconstriction

What does thromboxane A2 do?

Vasoconstriction and platelet aggregation

Which prostaglandin is the main inflammatory prostanoid?

PGE2

What type of receptors are prostaglandin receptors?

G-protein coupled receptors (GPCRs)

What second messenger do most prostaglandin receptors regulate?

cAMP

What does the EP1 receptor cause?

Bronchial and GI smooth muscle contraction

What does the EP2 receptor cause?

Bronchodilation and vasodilation

What does the EP3 receptor cause?

GI smooth muscle contraction; decreased gastric acid; increased mucus secretion

What does the EP4 receptor do?

Similar effects to EP2 and may inhibit leukocytes

What does one receptor type generally mean?

Same action in all tissues where expressed

What do multiple receptor types generally mean?

Different effects in different tissues

What are the main effects of leukotrienes?

Bronchoconstriction; increased vascular permeability; chemotaxis

What does LTB4 do?

Acts as a chemotactic agent for neutrophils

What do LTC4; LTD4; and LTE4 cause?

Bronchoconstriction and mucus production

What type of receptors are leukotriene receptors?

G-protein coupled receptors (GPCRs)

What receptor does LTB4 mainly act on?

B2 receptor

What is the main role of histamine in inflammation?

Increases blood vessel permeability

Why is increased vascular permeability important?

Allows white blood cells and proteins to enter tissues

What are the effects of histamine release?

Swelling; redness; pain

What do cytokines do during inflammation?

Increase vascular permeability and coordinate immune responses

How do cytokines help white blood cells?

Allow them to pass through vessel walls more easily

What are the main features of asthma?

Bronchoconstriction; airway inflammation; increased mucus production

How do leukotrienes contribute to asthma?

Cause bronchoconstriction and mucus secretion

What drugs can relieve asthma symptoms?

Bronchodilators; anti-inflammatory drugs; leukotriene antagonists; steroids

How do steroids reduce inflammation?

Inhibit phospholipase A2 and reduce arachidonic acid production

What inflammatory mediators are reduced by steroids?

Prostaglandins and leukotrienes

What causes gout?

Deposition of uric acid crystals in joints

What are the effects of gout?

Severe inflammation; pain; swelling

How is gout treated?

Anti-inflammatory drugs and drugs that reduce uric acid

What are DMARDs used to treat?

Rheumatoid arthritis

What is the purpose of DMARDs?

Slow disease progression and reduce immune-mediated joint damage

What does dolor mean?

Pain

What does rubor mean?

Redness

Which prostaglandin series is derived from arachidonic acid and contains two double bonds?

Prostaglandin G2 series

How do thromboxanes affect platelets?

Promote platelet aggregation

How do prostacyclins affect platelets?

Inhibit platelet aggregation