Lecture 1: Intro Inflammation

Question 1

Inhibits cytokines

Answer 1

Etanercept and Infliximab

Question 2

Inhibits prostaglandins

Answer 2

Aspirin and NSAID

Question 3

Inhibits leukotrienes

Answer 3

Zileuton and Zafirlukast

Question 4

What inhibits cytokines, prostaglandins, leukotrienes, cell adhesion molecules

Answer 4

Steroids

Question 5

What are the cardinal signs of actue inflammation

Answer 5

Red, heat, pain, swelling, LOF

Question 6

Physiological responses to ACUTE inflammation

Answer 6

Vasodilation, Increase in vascular permeability, accumulation of inflammatory cells (neutrophils)

Question 7

What is the main cell type associated with chronic and main characteristic

Answer 7

Macrophage (Monocyte), Fibrosis

Question 8

What is the main cell type associated with acute inflammation and its main characteristic

Answer 8

Neutrophils, and edema

Question 9

Histamine

Answer 9

A biogenic amine.

Stored in mast cells and basophils (non-mast cell sources in neurons and cells in the stomach).

Response is: vasodilation, increased vascular permeability, and pain.

Mechanism: Activation of GPCRs.

Pharmacology: antihistimines (H1 antagonists)

Question 10

Bradykinin

Answer 10

A peptide.

From endothelial cells.

Response: Vasodilation, increased microvessel permeability, pain.

Mechanism: Activation of GPCRs.

Pharmacology: BK receptor antagonists being tested

Question 11

Complement System

Answer 11

Plasma proteins.

Source by synthesis by liver circulating in blood.

Response: Chemotaxis, promote relase of mediators from neutrophil, increase vascular permeability, excessive activation may contribute to tissue injury.

Mechanism: Complement protein complex causes osmotic lysis, activation of GPCRs.

Question 12

C-Reactive Protein

Answer 12

A plasma protein.

Source by prodused in liver in response to cytokines, also produced in adipocytes.

Response: Acute-phase reactant, activates complement cascade, mediates phagocytosis, marker of inflammation.

Mechanism: Binds to phosphotidylcholine-containing substances in bacteria and damaged cells, calcium dependent binding.

Pharmacology: Too much CRP assoc with increased risk of diabetes, hypertension, and CV disease. No CRP inhibitors developed, Statins may be effective in reducing CRP levels

Question 13

What is acute phase reaction

Answer 13

In response to injury, local inflammatory cells secrete cytokines that cause the liver to increase or decrease production of various proteins. An acute phase protein is one whose plasma concentration changes from baseline by at least 25% during inflammation.

Question 14

What are the important cytokines

Answer 14

TNF-alpha, Interleukin-1 (IL-alpha, IL-beta)

Question 15

Cytokines

Answer 15

A secreted protein.

Source by nearly all cells.

Response: Stimulate acute phase reactants.
TNF-alpha: fever, sepsis
IL-1: fibroblast and lymphocyte proliferation, fever

Mechanism: Interaction with specific receptors to induce gene expression of number of proteins through activation of transcription factors, such as NF-kB and AP-1.

Pharmacology: Etanercept, inflixamab

Question 16

What are the results of activation of NFkB and AP-1

Answer 16

Increase cyclooxygenase (fever) and lipooxygenases. Increase adhesion molecule expression. Induce collagenase (fibrosis

Question 17

TNF-alpha

Answer 17

Stimulates acute phase reaction, fever, sepsis

Question 18

IL-1

Answer 18

Stimulates acute phase reaction, fibroblast and lymphocyte proliferation, fever

Question 19

Adenosine

Answer 19

A purine nucleoside formed from ATP breakdown.

Source: all cells.

Response: Increases extracellularly during injury and has an anti-inflammatory effect to inhibit cytokine action, receptor specific.

Mechanism: via specific GPCRs.

Pharmacology: A2 agonists, methotrexate (releases adenosine), Adenosine A3 antagonists in asthm/inhibit mediator release.

Question 20

Cell adhesion molecules

Answer 20

A family of proteins.

Source: endothelial cells, platelets, leukocytes.

Response: Leukocyte adhesion to endothelium, endothelial adhesion molecules contribute to recruitment of activated platelets.

Mechanism: contact molecules, calcium dependent.

Question 21

Oxygen-derived free radicals

Answer 21

Superoxide, hydroxy radicals. Source: all cells. Response: intracellular killing of bacteria by neutrophils. Mechanism: protein oxidation, lipid peroxidation, DNA mutations. Pharmacology: anti-oxidants like Vit C and E

Question 22

What are the lipid mediators

Answer 22

Prostaglandins. Leukotrienes. Steroids

Question 23

Prostaglandins

Answer 23

Source: almost all cells. Response: Vasodilation/vasoconstriction, pain, fever, platelet aggregation (via thromboxane). Mechanism: Activation of specific GPCRs. Pharmacology: NSAIDS

Question 24

Leukotrienes

Answer 24

Source: Macrophages and Neutrophils. Response: Increased vascular permeability, and Bronchoconstriction. Mechanism: GPCRs. Drugs: 5-lipoxygenase inhibitors (Zileuton), leukotriene receptor antagonist (Zafirlukast)

Question 25

Glucocorticoids

Answer 25

Source: Adrenal cortex. Response: Inhibition of cytokines, inhibition of phospholipase A2 (via annexin/lipocortin), inhibition of cyclooxygenase-2, inhibition of cell adhesion molecules. Mechanism: activation of nuclear receptors. Pharmacology: Steroids, most potent and effective agents for controlling chronic inflammatory diseases.

Question 26

Name the major drug groups for anti-inflammation

Answer 26

Steroids, NSAIDS, Leukotriene antagonists (Zafirlukast and zileuton), Inflammatory cytokine inhibitors (etanercept and infliximab)