Inner-city kids with high IL-6 show more asthma symptoms, susceptibility to mouse allergen
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Key takeaways:
- Asthma and high IL-6 levels were linked with increased BMI and elevated C-reactive protein levels.
- High IL-6 levels increase susceptibility to the effects of classroom exposure to mouse allergens.
Children who lived in inner cities and had high levels of IL-6 in their plasma appeared more likely to also have greater asthma symptoms, according to a study published in The Journal of Allergy and Clinical Immunology.
These high levels of IL-6 also appeared to increase susceptibility to the effects of exposure to mouse allergens in their classrooms on their lung function, Wanda Phipatanakul, MD, MS, director of the division of immunology research center at Boston Children’s Research Hospital, and colleagues wrote.
“IL-6 is an inflammatory cytokine that plays a role in obesity, metabolic dysfunction and asthma morbidity,” Phipatanakul, who also is the S. Jean Emans Professor of Pediatrics at Harvard Medical School, told Healio.
“No studies to date have evaluated whether a high peripheral blood IL-6 level increases susceptibility to the effects of indoor allergen exposure on asthma symptoms and lung function in urban children, and we sought to evaluate the role of classroom mouse allergen exposure,” she said.
Study design, results
The School Inner-City Asthma Studies (SICAS) involved 215 children aged 4 to 14 years (mean age, 8.6 years) with asthma, including 64% who reported using an inhaled corticosteroid during the previous 12 months. The cohort was 31% Black, 33% white and 53% Hispanic. Also, 55% had normal weight, 21% had overweight and 23% had obesity.
The researchers classified the children according to their baseline IL-6 levels, including: low, below the 50th percentile (< 0.013 pg/mL; n = 107); moderate, from the 50th to the 75th percentile (0.013-0.302 pg/mL; n = 54); and high, above the 75th percentile (> 0.302 pg/mL; n = 54).
Across these three groups, the researchers found significant differences in BMI percentile (P < .0001), plasma C-reactive protein (CRP) level (P = .0006) and blood neutrophil count (P = .0024).
Children who had high IL-6 levels had higher BMIs than those with moderate (P = .0018) or low (P < .0001) IL-6 levels as well as higher plasma CRP levels than those with moderate (P = .0077) or low (P < .0001) IL-6 levels, on average.
Additionally, children with low levels of IL-6 had lower blood neutrophil counts than children with high (P = .0005) and moderate (P = .0484) levels of IL-6, also on average.
There were no associations between IL-6 levels and type 2 inflammatory markers such as blood eosinophil count, allergic sensitization or fractional exhaled nitric oxide, according to the researchers.
The IL-6 groups did not show any differences in the number of days with asthma symptoms, but the children with high IL-6 levels had an increased rate of days with asthma symptoms compared with the moderate (incidence rate ratio [IRR] = 1.74; 95% CI, 1.1-2.77; P = .0187) and the low (IRR = 1.83; 95% CI, 1.21-2.77; P = .0043) groups.
The researchers further said that it was interesting that children in the high group who were exposed to increasing levels of mouse allergen had lower ratios of FEV1 to forced vital capacity (FEV1/FVC) than the moderate (B = –0.0044; 95% CI, –0.0073 to –0.0015; P = .0028) and the low (B = –0.0042; 95% CI, –0.007 to –0.0013; P = .0039) groups.
“There was a clear association with classroom mouse allergen exposure, IL-6 levels and decline in lung function, suggesting interactions,” Phipatanakul said. “This has never been reported before.”
Even small decreases in FEV1/FVC due to allergen exposure can significantly affect respiratory health, the researchers added, especially among children with preexisting respiratory conditions or who are at risk for developing these conditions.
Conclusions, next steps
Based on these findings, the researchers wrote, high levels of IL-6 appear to increase susceptibility to the effects that classroom exposure to mouse allergen has on lung function.
The researchers also noted that the SICAS study detected mouse allergen in 99% of classrooms and that there was a significant association between exposure to mouse allergen and worsening asthma symptoms regardless of sensitization.
Further, the researchers noted that how peripheral blood IL-6 is involved in the pathogenesis of asthma is not entirely clear, but recent advances suggest a direct link between IL-6 and airway inflammation. Asthma treatment that blockades IL-6 has potential, the researchers added.
“It helps to understand that patients with high potential inflammatory biomarkers such as IL-6 and certain exposures may have worse asthma,” Phipatanakul said. “These could be targets for intervention.”
Still, the researchers called for further mechanistic studies to determine the clinical relevance of the increases in susceptibility to allergen exposure in the airway with high levels of IL-6.
Changes in policy may improve outcomes as well, Phipatanakul said.
“Reducing exposures and evaluating biomarkers and clinical trials utilizing targets on these biomarkers may be of interest,” she said.
For more information:
Wanda Phipatanakul, MD, MS, can be reached at wanda.phipatanakul@childrens.harvard.edu.
Perspective
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Stephanie Lovinsky-Desir, MD, MS
The findings from this study support existing knowledge that IL-6 may serve as a biomarker of inflammatory diseases such as asthma. What is interesting is that the high IL-6 levels did not seem to correlate with the typical allergic biomarkers that we would expect, such as blood eosinophil count, allergic sensitization and allergic airway inflammation. Thus, the IL-6 biomarker may be distinguishing a different, unique population of children with asthma who have high exposure to allergens in their environment.
As part of the NIH-funded Childhood Asthma in Urban Settings (CAUSE) network, our group is studying the role of the IL-6 receptor in pediatric asthma as well. So, the findings from this study are closely aligned and complementary to the work that we are doing. The overall goal is to better understand which allergic pathways are activated in which specific groups of children so we can better understand who will benefit most from targeted therapeutic interventions.
I do not think that the findings from this study are ready for prime time, patient care implementation yet. Rather, this is one building block that will help us better identify targeted biomarkers and related therapies for the future of pediatric asthma care. An IL-6 receptor inhibitor has already been developed. Now we need to use the findings from this study and others to better understand who will benefit the most from this new medication.
Larger studies need to be conducted to better understand appropriate thresholds or cutoff values for high vs. low IL-6 levels. These studies will be helpful as we think about the role of IL-6 receptor inhibitors for management of pediatric asthma.
One of the most striking observations in this study is that 99% of the classrooms had positive exposure to mouse allergen. Schools are supposed to be a safe space for children. Yet, this study demonstrates that the environments where children are learning can be hazardous to their health. Thus, it is important to use studies such as this to advocate to heighten efforts to improve air quality and allergen mitigation in communities where children are disproportionately burdened by asthma.
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