Leukotrienes

• Leukotrienes are eicosanoids derived from arachidonic acid via the lipoxygenase (LOX) pathway.
• Leukotrienes are primarily involved in immune and inflammatory responses.
• These three groups are collectively called eicosanoids, derived from arachidonic acid via the cyclooxygenase (COX) or lipoxygenase pathways.

Major Leukotrienes:

1. LTB4 (Leukotriene B4):

   • Functions: Acts as a potent chemotactic agent, attracting neutrophils to sites of inflammation.

2. LTC4, LTD4, LTE4 (Cysteinyl Leukotrienes):

   • Functions: Induce bronchoconstriction, increase vascular permeability, and contribute to inflammatory responses.

Synthesis:

• Immune Cells Activation: Upon stimulation, cells like mast cells, eosinophils, and macrophages release arachidonic acid.
• LOX Pathway: 5-LOX converts arachidonic acid into leukotriene A4 (LTA4), which is further transformed into LTB4 or conjugated with glutathione to form LTC4, LTD4, and LTE4.

Arachidonic acid  →  (5-lipoxygenase)  →  Leukotriene A4  →  LTB4, LTC4, LTD4, LTE4.

Physiological and Pathological Roles:

• Asthma and Allergies: Cysteinyl leukotrienes mediate bronchoconstriction and increased mucus production.
• Inflammation: LTB4 recruits and activates leukocytes, amplifying the inflammatory response.
• Autoimmune Diseases: Involved in the pathogenesis of conditions like rheumatoid arthritis.

Pharmacological Effects of Leukotrienes:

• Bronchoconstriction: Cause tightening of airway muscles, contributing to asthma and allergic reactions.
• Increased Vascular Permeability: Promote leakage of fluids into tissues, leading to edema.
• Chemotaxis: Attract immune cells like neutrophils to sites of inflammation.
• Mucus Secretion: Stimulate mucus production in the respiratory tract.
• Pain Sensitization: Enhance pain perception during inflammatory responses.

Drug targets:

• 5-lipoxygenase inhibitor: Zileuton (used in asthma).
• Leukotriene receptor antagonists: Montelukast, Zafirlukast (for asthma prophylaxis).

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