What is the body attempting to do when it produces leukotrienes (leukotrienes)?

What Is Your Body Attempting to Do When It Produces Leukotrienes?

When your body produces leukotrienes, it is mounting an inflammatory response to perceived threats or injury, attempting to recruit immune cells, increase vascular permeability, constrict smooth muscle, and promote tissue defense—though this response often becomes pathologic in conditions like asthma and allergic diseases. 1

Primary Physiologic Functions

Leukotrienes are lipid mediators synthesized from arachidonic acid through the 5-lipoxygenase pathway in inflammatory cells, particularly mast cells, eosinophils, and neutrophils 2, 3. Your body produces these molecules as part of its innate immune defense system with several key objectives:

Immune Cell Recruitment and Activation

• Leukotriene B4 (LTB4) functions as one of the most potent chemoattractants for leukocytes, drawing neutrophils and other inflammatory cells to sites of injury or infection 4, 3
• This chemotactic activity represents the body's attempt to concentrate immune defenses at specific locations where threats are detected 5

Vascular and Tissue Responses

• Cysteinyl leukotrienes (LTC4, LTD4, LTE4) dramatically increase microvascular permeability, allowing plasma proteins and immune cells to exit blood vessels and enter tissues 4, 5
• These same cysteinyl leukotrienes cause potent smooth muscle contraction, particularly in airways, which the body may use as a protective mechanism to limit pathogen entry 1, 2
• The body induces airway edema and mucus production through leukotriene action, theoretically to trap and expel foreign materials 1, 2

Context-Specific Inflammatory Responses

In Allergic Reactions and Asthma

• During allergen exposure, mast cells degranulate and release leukotrienes as part of both early and late-phase allergic responses 1
• In exercise-induced bronchoconstriction, the body produces leukotrienes in response to hyperosmolar conditions created by water loss from rapid breathing, with the hyperosmolar environment triggering mast cell degranulation 1
• Cysteinyl leukotrienes are released from nasal mucosa after allergen exposure and mediate symptoms of allergic rhinitis including nasal obstruction 2

In Lung Injury and Chronic Disease

• In premature infants developing chronic lung disease, cysteinyl leukotrienes C4, D4, and E4 are elevated 10- to 20-fold compared to controls, representing the body's inflammatory response to lung injury 1
• The body produces leukotriene B4 in combination with chemokines like IL-8 to induce neutrophil chemotaxis during acute lung injury 1

When the Response Becomes Pathologic

The critical issue is that while leukotriene production represents the body's attempt at defense and repair, this response frequently becomes maladaptive and causes disease rather than protection 6, 4:

• In asthma, leukotriene-mediated airway edema, smooth muscle contraction, and altered cellular activity create the pathophysiology of the disease rather than protecting the airways 1, 2
• Leukotrienes contribute to tissue injury in inflammatory bowel disease, rheumatoid arthritis, and psoriasis, demonstrating that this inflammatory mechanism extends beyond respiratory disease 6, 3, 5
• The body's leukotriene response can induce neutrophil-dependent increased microvascular permeability that contributes to tissue damage 4

Clinical Implications

This understanding explains why leukotriene modifiers (receptor antagonists like montelukast and zafirlukast, or synthesis inhibitors like zileuton) are effective therapeutic agents 1, 2:

• These medications work by blocking what the body is attempting to do—they interrupt the inflammatory cascade that, while intended as protective, actually causes disease symptoms 3, 5
• Leukotriene receptor antagonists improve asthma control by preventing cysteinyl leukotrienes from binding to CysLT1 receptors on airway smooth muscle cells and inflammatory cells 2
• The efficacy of these agents across multiple inflammatory diseases (asthma, allergic rhinitis, inflammatory bowel disease) confirms that leukotriene production represents a universal inflammatory mechanism 6, 7

In essence, leukotriene production reflects your body's attempt to defend itself through inflammation—recruiting immune cells, increasing vascular permeability, and contracting smooth muscle—but this ancient protective mechanism frequently overshoots in modern allergic and inflammatory diseases, causing more harm than benefit.