High Interleukin (IL)-6 is Associated with Lower Lung Function and Increased Likelihood of Metabolic Dysfunction in Asthma

Abstract

Introduction Asthma is a complex condition characterized by airway inflammation. Interleukin-6 (IL-6) plays a significant role in asthma pathogenesis through its effects on T cells and its association with pro-inflammatory responses. Both lung and circulating IL-6 levels are elevated in asthma. IL-6 is positively associated with disease severity, frequent exacerbations, and impaired lung function, all of which can be observed clinically. We developed an IL-6 cut-off model to examine the association between high IL-6, race, high body mass index (BMI), metabolic disease, and asthma severity as assessed by reduced lung function. Methods This study utilized the Coronary Artery Risk Development in Young Adults (CARDIA) database, comprised of 5115 adults, to investigate the relationship between IL-6 levels, asthma, race, and metabolic dysfunction. A "healthy" subset of 427 patients was used to compute the IL-6 cut-off. IL-6 levels within detection limits (0.15–12 pg/mL) were analyzed. The IL-6 cut-off was determined using the 95th percentile of log-transformed IL-6 values for lean (BMI < 25) and healthy individuals. Specific cut-offs were established for racial groups. Statistical analyses involved comparing patient characteristics between high and low IL-6 groups, regression analyses, and assessment of factors influencing lung function changes. Results Using an IL-6 cut-off of 4.979 pg/mL, the cohort was divided into high and low IL-6 groups. High IL-6 correlated with Black race, higher BMI, hypertension, and markers of metabolic dysfunction, e.g., elevated HbA1c, C-reactive protein (CRP), and reduced lung function. Multivariable analysis linked high IL-6 with male gender, high BMI, Black race, HbA1c, CRP, and inversely with lung function and total cholesterol. Obesity showed a consistent positive association with elevated IL-6, regardless of the presence or absence of asthma. Patients with asthma and high IL-6 were more likely to be Black and showed increased CRP. Lung function was lowest in non-lean, high IL-6 patients with asthma, with similar trends in non-lean (BMI ≥ 25) patients without asthma. Conclusion This study underscores the significant association between IL-6, asthma, obesity, and metabolic dysfunction. Elevated IL-6 correlates with asthma severity, particularly in individuals with obesity. Future research should explore anti-IL-6 therapies for specific phenotypes, such as obesity-related asthma. These findings advance our understanding of asthma and the role of IL-6 in its pathogenesis.