Lipid Mediators of Inflammation

Question 1

EICOSANOIDS:
What are the 3 main classes?
→ What do they do?

What are the 2 enzymes involved in its formation?

How are Prostanoids formed from Phospholipids?

Answer 1

• Prostaglandins, Thromboxanes, Leukotrienes
  → Powerful inflammatory actions
• • Cyclooxygenases (COX) - Forms Prostaglandins/PG and Thromboxanes/TX (Prostanoids)
  • Lipooxygenases (LOX) - Forms Leukotrienes/LT and Lipoxins
• 1. Phospholipids → ARACHIDONIC ACID (AA)
     
     2. AA → Prostanoids (via COX) - Rate Limiting Step

Question 2

CYCLOOXYGENASE:
What are the 3 types of COX enzymes? Describe their properties

What are the 3 types of substances formed from COX?

What drug inhibits TXA2 production?

Answer 2

• • COX-1 - Always ACTIVE, Responsible for TPR regulation, Renal blood flow, Platelet aggregation and Gastric cytoprotection
  • COX-2 - Needs to be STIMULATED Responsible for Inflammatory responses (Pain and Fever)
  • COX-3 - Variant of COX-1, Responsible for Pain perception in the CNS
• • Classical Prostaglandins
  o PGE2 - Bronchoconstriction, Inhibits platelet aggregation
  o PGF2a - Bronchoconstriction, Uterine contraction
  • Prostacyclin (PGI2)
  • Thromboxane A2 (TXA2)
• Aspirin

Question 3

LIPOOXYGENASE:
What does LOX convert AA into?
→ What is needed for this step?

What does this 1st product then become?

What substances are made at the onset of inflammation compared to its resolution?

What is the function of Lipoxins?

Answer 3

• 5-HPETE
  → FLAP
• Leukotriene A4
• Goes from Pro-inflammatory PG and LTs at onset to Anti-inflammatory Lipoxins at resolution
• Recruit Monocytes to clear inflamed site of dead neutrophils as well, Regulate activation levels and increase phagocytosis of neutrophils

Question 4

Where do PGs, TXs, and LTs act?

What do the LTs lead to?

Leukotriene Receptor Antagonist (LTRA):
What does it do?

What are they used for?

What are its side-effects?

How do LTs compare to Histamine?

Poly-unsaturated Fatty Acids (PUFA):
What do Fish oils have a role in?

What does ↑PUFA lead to?

Answer 4

• • PGs at DP, FP, IP, EP receptors
  • TXs at TP receptors
  • LTs at BLT receptors
• Bronchoconstriction, ↑Mucous secretion, ↑Vessel permeability, Oedema

• Block receptors for Cysteinyl LTs
• Prevention of mild/moderate Asthma, Bronchoconstrictor effects of allergens, and Exercise/NSAID-induced asthma
• GI upset, Dry mouth, Thirst, Rashes, Oedema, Irritability
• Is much more potent

• Anti-inflammation
• ↓AA