Leukotrienes are potent chemical signals that cells within the immune system release, most often as part of an inflammatory response. These molecules are a normal part of the body’s defense mechanisms, helping to protect it from things it perceives as harmful. When the body encounters certain triggers, such as allergens or pathogens, the production of these chemicals initiates a cascade of events designed to isolate and deal with the threat.
How Leukotrienes Are Produced
Leukotrienes originate from a fatty acid called arachidonic acid, which is a common component found within the membranes of cells. Their production is not constant but is initiated by specific triggers, such as an injury or the presence of an allergen. This process begins when an enzyme named 5-lipoxygenase (5-LO) is activated, starting a biochemical pathway that transforms arachidonic acid into a series of leukotriene molecules.
The initial steps of this synthesis take place near the cell’s nucleus. An enzyme called phospholipase A2 first releases arachidonic acid from the cell’s membrane phospholipids. This free arachidonic acid is then acted upon by 5-LO, which catalyzes a two-step reaction to create an unstable intermediate molecule known as leukotriene A4 (LTA4).
From this point, the pathway can branch. Depending on the type of cell and the specific enzymes it contains, LTA4 can be converted into different types of leukotrienes. For example, the enzyme LTA4 hydrolase converts LTA4 into leukotriene B4 (LTB4). Alternatively, in cells like mast cells and eosinophils, an enzyme called LTC4 synthase will conjugate LTA4 with glutathione to form leukotriene C4 (LTC4), the first in a subgroup called the cysteinyl leukotrienes.
The Function of Leukotrienes in the Body
Once produced and released, leukotrienes act as local hormones that orchestrate various aspects of the inflammatory response. One of their primary actions is bronchoconstriction, the tightening of the smooth muscles that line the airways of the lungs. The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are particularly potent in this regard, causing the air passages to narrow, which can make breathing more difficult.
Another primary function is increasing vascular permeability. Leukotrienes cause the small blood vessels, or capillaries, to become more porous. This “leaky” state allows fluid, proteins, and plasma to move from the bloodstream into the surrounding tissues. The accumulation of this fluid is what leads to swelling, or edema, a common sign of localized inflammation.
Leukotrienes also serve as chemical messengers in a process called chemotaxis. Leukotriene B4 (LTB4) is a chemoattractant, meaning it sends out a signal that recruits other immune cells, particularly neutrophils, to the site of injury or infection. These recruited cells are frontline defenders that help to engulf pathogens, clear away cellular debris, and contribute to the overall immune defense and tissue repair.
Finally, these mediators stimulate the glands in the respiratory tract to produce and secrete more mucus. While mucus production is a normal protective mechanism to trap inhaled particles, an overproduction stimulated by leukotrienes can contribute to congestion and obstruction within the airways.
Leukotrienes and Associated Health Conditions
The biological actions of leukotrienes are directly responsible for the symptoms of several common health conditions involving allergy and inflammation. In asthma, the effects of leukotrienes are particularly pronounced. The bronchoconstriction they induce causes airway narrowing that leads to wheezing, chest tightness, and shortness of breath, while increased mucus secretion and fluid leakage contribute to congestion and obstruction.
Allergic rhinitis, or hay fever, is another condition heavily influenced by leukotrienes. When a person with allergies inhales a trigger, immune cells in the nasal passages release these chemicals. They then cause the blood vessels in the nose to become leaky, leading to nasal congestion, and stimulate mucus overproduction, resulting in a runny nose.
Beyond the respiratory system, leukotrienes are involved in other inflammatory disorders. They are implicated in skin conditions like atopic dermatitis (eczema) and chronic hives (urticaria). In these cases, leukotriene activity in the skin contributes to the swelling, redness, and itchiness that define these conditions.
Medications That Target Leukotrienes
Given their direct role in causing symptoms, a class of medications known as leukotriene modifiers has been developed to counteract their effects. These drugs work in one of two primary ways. The most common type is the leukotriene receptor antagonists, which include drugs like montelukast and zafirlukast. These medications function by selectively blocking the CysLT1 receptor, the specific cell-surface receptor that cysteinyl leukotrienes bind to. By occupying this receptor, the antagonist prevents the leukotriene molecule from initiating the inflammatory response in the target cell.
Another approach is to inhibit the production of leukotrienes in the first place. This is the mechanism of synthesis inhibitors, such as the drug zileuton. Zileuton works by directly blocking the 5-lipoxygenase (5-LO) enzyme. Since 5-LO is the enzyme that initiates the entire production cascade from arachidonic acid, inhibiting it effectively stops the synthesis of all types of leukotrienes.
Leukotriene modifiers are primarily prescribed as long-term controller or preventative therapies for chronic conditions like asthma and allergic rhinitis. They are not intended for use as fast-acting rescue treatments during an acute asthma attack, as their onset of action is too slow to provide immediate relief from severe bronchoconstriction. Instead, when taken consistently, they help to manage the underlying inflammation and reduce the frequency and severity of symptoms over time.