Allergen-induced increases in adipocytokines: linking airway and systemic inflammation in asthma

To the Editor: Metabolic dysregulation is increasingly implicated in asthma pathogenesis, defining inflammatory phenotypes and influencing therapeutic responses.1 Adipocytokines including interleukin-6 (IL-6), leptin, adiponectin, and resistin, play critical roles in metabolic regulation, systemic inflammation, and insulin sensitivity.2 Blood IL-6, an adipocytokine, is associated with asthma severity, metabolic dysfunction, and cardiovascular disease.1,3 In the Severe Asthma Research Program (SARP), elevated blood IL-6 was associated with asthma exacerbations, reduced lung function, and higher rates of diabetes mellitus and hypertension.1 Although obesity and metabolic dysfunction often coexist, only 38% of obese patients with asthma in SARP had high IL-6, and the lack of correlation between plasma and sputum IL-6 suggests elevated blood IL-6 may originate outside the airways.1 This led to the “outside-in” hypothesis, where systemic inflammation drives airway inflammation.1 Conversely, acute allergen-induced airway inflammation may impact systemic inflammation, supporting an “inside-out” mechanism.4 Non–IL-6 adipocytokines are elevated in obese asthma; however, airway and blood compartment relationships during exacerbations remain unclear.5 To investigate this, we employed an allergen-challenge model to test the hypothesis that increased levels of adipocytokines in the airway following allergen challenge are associated with higher blood adipocytokine levels.