What is the function of the leukotrienes?

October 7, 2025 •

4 min read

Leukotrienes are potent pro-inflammatory lipid mediators, and their overproduction is linked to significant pathological features of asthma and allergies. But what is the function of the leukotrienes in both normal physiological processes and in disease states?

Quick Summary

Leukotrienes are lipid compounds synthesized from arachidonic acid that play a central role in inflammation and allergic reactions. They cause bronchoconstriction, increase vascular permeability, stimulate mucus secretion, and recruit inflammatory cells to affected tissues.

Key Points

Mediators of Inflammation: Leukotrienes are potent lipid mediators derived from arachidonic acid, released by various immune cells like mast cells, eosinophils, and neutrophils during inflammation and allergic reactions.
Subtypes and Specific Functions: They consist of two main groups: LTB4, which is a powerful chemotactic agent for neutrophils, and Cysteinyl Leukotrienes (CysLTs), which cause bronchoconstriction and increase vascular permeability.
Role in Asthma: CysLTs are major contributors to the pathophysiology of asthma by causing airway smooth muscle contraction, increased mucus secretion, and airway edema.
Therapeutic Targets: In pharmacology, drugs called leukotriene modifiers target these functions by either inhibiting leukotriene synthesis (e.g., Zileuton) or blocking their receptors (e.g., Montelukast).
Not for Acute Attacks: Leukotriene modifiers are used for the long-term, prophylactic management of conditions like asthma and allergies, not for treating acute episodes.
Contribution to Allergic Rhinitis: Leukotrienes are responsible for the nasal congestion associated with allergic rhinitis, an effect not fully managed by antihistamines alone.

The Biochemistry and Synthesis of Leukotrienes

Leukotrienes are a class of lipid mediators derived from the essential fatty acid arachidonic acid. Their synthesis is a highly regulated process initiated within leukocytes and other immune cells in response to activating stimuli like pathogens or allergens.

The 5-Lipoxygenase (5-LOX) Pathway

Upon cellular activation, arachidonic acid is released from cell membranes and acted upon by the enzyme 5-lipoxygenase (5-LOX). This process is facilitated by the 5-lipoxygenase-activating protein (FLAP). 5-LOX converts arachidonic acid into the unstable intermediate leukotriene A4 (LTA4). From LTA4, two primary, biologically active types of leukotrienes are produced through different enzymatic routes:

Leukotriene B4 (LTB4): Synthesized by the enzyme LTA4 hydrolase, LTB4 is primarily produced by neutrophils and other inflammatory cells. It is a powerful chemoattractant.
Cysteinyl Leukotrienes (CysLTs): The enzyme LTC4 synthase conjugates LTA4 with glutathione to form LTC4, the precursor to LTD4 and LTE4. These are referred to as cysteinyl leukotrienes due to a shared cysteine residue and are predominantly produced by mast cells and eosinophils.

The Diverse Functions of Leukotrienes

The specific functions of leukotrienes depend heavily on their subtype, but they are generally involved in amplifying and propagating the inflammatory and immune response. While this is a critical defense mechanism, excessive or inappropriate production can lead to significant pathology.

Functions of Leukotriene B4 (LTB4)

LTB4's main function is to serve as a potent chemotactic agent, directing the movement of immune cells to sites of inflammation or infection. Its key functions include:

Recruitment of White Blood Cells: It attracts neutrophils, monocytes, and T-lymphocytes to inflamed tissues.
Activation of Phagocytes: It enhances the phagocytic activity of macrophages, allowing them to better engulf and destroy pathogens.
Modulation of Inflammatory Duration: It can promote the resolution of inflammation by activating pathways that break down fatty acid derivatives like LTB4 itself.

Functions of Cysteinyl Leukotrienes (CysLTs)

CysLTs mediate many of the characteristic symptoms of allergic reactions and asthma. They exert their effects through G protein-coupled receptors, CysLT1 and CysLT2, found on various cells. Key CysLT functions include:

Bronchoconstriction: They are powerful constrictors of airway smooth muscle, leading to narrowing of the airways and difficulty breathing. This is the basis for their historical name, "slow-reacting substance of anaphylaxis" (SRS-A).
Increased Vascular Permeability: By increasing the permeability of blood vessels, they cause fluid leakage into tissues, resulting in edema and swelling.
Mucus Secretion: CysLTs stimulate mucus-secreting cells, leading to hypersecretion of thick mucus, which further obstructs airways.
Eosinophil Recruitment: They promote the recruitment and activation of eosinophils in the airways, a hallmark of allergic inflammation.

Role of Leukotrienes in Disease

Leukotrienes are crucial mediators in several inflammatory and allergic diseases, and blocking their action is a primary therapeutic strategy. The following list highlights their role in common conditions:

Asthma: Excessive CysLT production is a significant driver of the symptoms of asthma, including bronchoconstriction, inflammation, and mucus production. This makes them a key target for therapy.
Allergic Rhinitis: In allergic rhinitis (hay fever), leukotrienes contribute to the nasal congestion by causing vasodilation and plasma extravasation within the turbinates. They are a major reason for the limited effectiveness of antihistamines alone for congestion.
Anaphylaxis: CysLTs are components of the slow-reacting substance of anaphylaxis, causing severe bronchoconstriction and increased vascular permeability during this life-threatening allergic reaction.
Other Inflammatory Conditions: LTB4's chemotactic properties implicate leukotrienes in chronic inflammatory diseases like rheumatoid arthritis and psoriasis, where immune cell recruitment plays a central role.

Therapeutic Modulation via Leukotriene Modifiers

In pharmacology, medications known as leukotriene modifiers are used to counteract the effects of these inflammatory mediators. These drugs fall into two main categories, synthesis inhibitors and receptor antagonists, which act at different points in the leukotriene pathway.

Comparison of Leukotriene Modifiers


Feature	Leukotriene Synthesis Inhibitors (e.g., Zileuton)	Leukotriene Receptor Antagonists (e.g., Montelukast)
Mechanism of Action	Inhibits the 5-lipoxygenase (5-LOX) enzyme, blocking the formation of all leukotrienes.	Selectively blocks the CysLT1 receptor, preventing cysteinyl leukotrienes from binding and activating it.
Targeted Leukotrienes	LTB4, LTC4, LTD4, and LTE4.	Primarily targets the effects of LTD4, which has the highest affinity for the CysLT1 receptor.
Therapeutic Scope	Broad effects on all leukotriene-mediated processes, including neutrophil and eosinophil activity.	Narrower, primarily blocks the effects mediated by CysLT1 receptors, such as bronchoconstriction.
Clinical Use	Used for the prophylactic treatment of chronic asthma.	Used for chronic asthma, exercise-induced asthma, and allergic rhinitis.
Monitoring	Requires monitoring of liver enzymes due to potential hepatotoxicity.	Less frequent monitoring required, but mental health side effects are a concern.

Conclusion: The Double-Edged Role of Leukotrienes

In summary, leukotrienes are crucial lipid mediators that play a significant but complex role in both a healthy immune response and in pathological inflammatory conditions. By orchestrating the movement of immune cells and modulating vascular function, they help the body defend against pathogens. However, when their production or signaling becomes excessive or dysregulated, as in asthma and allergic diseases, they cause harmful effects such as bronchoconstriction, edema, and mucus hypersecretion. The development of leukotriene modifiers, which either inhibit synthesis or block receptors, provides important pharmacological tools for managing these conditions and mitigating the negative consequences of overactive leukotriene function. Understanding the delicate balance of leukotriene signaling is key to developing effective treatments for a wide range of inflammatory and allergic disorders.

Frequently Asked Questions

Both leukotrienes and prostaglandins are eicosanoids derived from arachidonic acid, but they are produced through different enzymatic pathways (5-lipoxygenase for leukotrienes and cyclooxygenase for prostaglandins) and mediate different aspects of the inflammatory response.

Cysteinyl leukotrienes (CysLTs) bind to receptors on airway smooth muscle cells, causing them to contract and constrict the airways. They also increase mucus secretion and vascular permeability, contributing to airway inflammation and obstruction.

Leukotriene modifiers are a class of medications that counteract the effects of leukotrienes. They include leukotriene receptor antagonists (e.g., Montelukast) that block receptors and leukotriene synthesis inhibitors (e.g., Zileuton) that prevent production.

No, leukotriene modifiers are primarily used for the long-term, preventive control of asthma and allergies. They are not fast-acting and should not be used as rescue medication during an acute asthma attack.

Leukotrienes are produced mainly by cells of myeloid origin, including mast cells, eosinophils, basophils, monocytes, and neutrophils, especially upon activation by allergens or pathogens.

Yes, cysteinyl leukotrienes (CysLTs) contribute to the severe bronchoconstriction, plasma extravasation, and other symptoms characteristic of anaphylaxis.

In allergic rhinitis, leukotrienes contribute significantly to nasal congestion by increasing vascular permeability and fluid leakage in the nasal passages. This is why antihistamines alone may not relieve congestion.