From the Guidelines
Interleukin-13 (IL-13) is the primary interleukin that activates fractional exhaled nitric oxide (FeNO) production in the airways.
Background
The relationship between FeNO and airway inflammation, particularly eosinophilic inflammation, is well-established 1. FeNO is used as a biomarker for assessing airway inflammation and monitoring response to therapies.
Mechanism of Action
IL-13 stimulates the expression of inducible nitric oxide synthase (iNOS) in bronchial epithelial cells, leading to increased production of nitric oxide that can be measured in exhaled breath. This process is particularly important in type 2 inflammation seen in asthma and other allergic airway diseases.
Clinical Applications
The measurement of FeNO is useful in determining the likelihood of steroid responsiveness in individuals with chronic respiratory symptoms possibly due to airway inflammation 1. Elevated FeNO levels typically indicate active IL-13-mediated inflammation in the airways, which helps clinicians identify patients who might benefit from targeted therapies and monitor treatment effectiveness.
Key Points
- IL-13 has a dominant effect on FeNO production compared to other interleukins like IL-4.
- FeNO measurement is a useful biomarker for assessing type 2 airway inflammation.
- Targeted therapies like biologics (e.g., dupilumab or lebrikizumab) may be beneficial for patients with elevated FeNO levels, indicating active IL-13-mediated inflammation.
From the FDA Drug Label
Dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE. In asthma subjects, fractional exhaled nitric oxide (FeNO) and circulating concentrations of eotaxin-3, total IgE, allergen specific IgE, TARC, and periostin were decreased relative to placebo
The interleukin that activates Fractional exhaled Nitric Oxide (FeNO) is not directly stated in the label. However, it can be inferred that IL-4 and IL-13 are involved in the inflammatory response that includes the release of nitric oxide.
- IL-4 and IL-13 are the interleukins that, when inhibited, result in a decrease in FeNO. 2
From the Research
Interleukin Activation of FeNO
- The activation of Fractional exhaled Nitric Oxide (FeNO) is associated with interleukin-13 (IL-13) 3, 4, 5, 6.
- IL-13 synergizes with interleukin-4 (IL-4) in inducing IgE production and also promotes nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion 3, 4.
- IL-13 is a key cytokine involved in the pathophysiology of type 2 asthma and is associated with increased FeNO levels 5, 6.
- The use of anti-IL-4/IL-13 agents, such as dupilumab, has been shown to decrease FeNO levels in patients with severe asthma 3, 4, 6.