From the Guidelines
Elevated Interleukin-4 (IL-4) levels, indicative of a T-helper 2 (Th2) response, at 51, suggest an active allergic or autoimmune condition that may require treatment with corticosteroids, antihistamines, or immunomodulators to downregulate the Th2 response. Interleukin-4 (IL-4) is a cytokine primarily produced by activated T helper 2 (Th2) cells and is a key regulator of the Th2 immune response 1. This elevation in IL-4 levels indicates a strong Th2-mediated immune response, which can be associated with various conditions, including allergic reactions, parasitic infections, or certain autoimmune diseases.
Key Points to Consider
- The Th2 response is characterized by the production of cytokines such as IL-4, IL-5, and IL-13, which promote allergic inflammation and are often elevated in conditions like asthma 1.
- Elevated IL-4 levels can lead to increased IgE production, mast cell development, and further Th2 cell differentiation, creating a feedback loop that perpetuates allergic inflammation.
- Treatment of conditions with elevated IL-4 levels depends on the underlying cause but may include avoiding triggers, using antihistamines like cetirizine 10mg daily, corticosteroids like fluticasone nasal spray 50mcg 1-2 sprays per nostril daily, or specific immunomodulators to downregulate the Th2 response.
- Monitoring IL-4 levels during treatment can help assess therapeutic effectiveness in conditions with Th2 dominance, as seen in some cases of refractory asthma where IL-4 and other Th2-type cytokines are increased 1.
Clinical Implications
- In the context of refractory asthma, elevated IL-4 levels may indicate a subset of patients with persistent eosinophilic inflammation despite high-dose corticosteroid therapy 1.
- The presence of neutrophils in higher quantities in the airways of patients with refractory asthma suggests a different type of inflammatory process that may be less responsive to corticosteroids 1.
- Understanding the role of IL-4 in the pathogenesis of allergic and autoimmune conditions can guide the development of targeted therapies to modulate the Th2 response and improve patient outcomes.
From the Research
Significance of Elevated Interleukin-4 (IL-4) Level and T-helper 2 (Th2) Response
- An elevated IL-4 level, indicative of a T-helper 2 (Th2) response, is associated with the development of allergic asthma 2, 3, 4.
- Th2 cells play a central role in orchestrating the allergic and asthmatic inflammatory response pathways, with 80% of children and 60% of adult asthma cases linked to an unwarranted Th2 cell response against respiratory allergens 2.
- A distinct subpopulation of pathogenic Th2 cells, characterized by coexpression of CRTH2, CD49d, and CD161, is associated with allergic disorders and exhibits numerous functional attributes distinct from conventional Th2 cells 3, 4.
Implications of Th2 Response in Asthma
- Targeting essential components of Th2-type inflammation using neutralizing antibodies against key Th2 modulators has become an attractive option for asthmatic patients with moderate to severe symptoms 2.
- Allergen immunotherapy, also known as desensitization, aims to redirect the allergen-specific T cells response from a Th2-type profile to a tolerogenic one 2.
- Blood eosinophil count and fractional exhaled nitric oxide (FeNO) are recognized as markers of Th2-type inflammation, with FeNO being associated with more frequent hospital admissions and more working days lost in severe asthmatics 5.
Therapeutic Management of Allergic Asthma
- The relevance of blood eosinophil count and FeNO in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy has been investigated, with blood eosinophils acting as a predictor of response to omalizumab 5.
- Pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and leukotriene modifiers (LTMs) have been studied, with the most consistent results found for the FCER2 gene and poor ICS response 6.