A multinational research team uncovered a potential link between cystic fibrosis transmembrane conductance regulator (CFTR) function, interleukin-1β (IL-1β), and airway nitric oxide (NO) in cystic fibrosis (CF).

“Here, we demonstrate that treatment with ivacaftor, a drug that improves the opening probability of the CFTR channel rapidly, reduces airway IL-1β concentrations and that this reduction is associated with parallel improvements in lung function and airway NO concentrations,” said the authors of the study published in the Journal of Cystic Fibrosis.

Treatment with the CFTR-targeted drug ivacaftor (Kalydeco®) decreased the levels of IL-1β in the sputum of patients with CF (n=11) at first follow-up (1-3 months). No other IL-1 or Th17-associated cytokines, including IL-1α, IL-1RA, IL-6, IL-8, or IL-17a, were altered in response to ivacaftor treatment.

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IL-1β concentration was correlated with L-arginine/asymmetric dimethylarginine (ADMA) ratio in patients’ sputum, as well as with forced expiratory volume in 1 second percent predicted, lung clearance index, and fractional exhaled NO (FeNO).

The authors observed a negative correlation between changes in sputum IL-1 β from baseline and changes in the L-arginine/ADMA ratio. Hence, they suggest that downregulation of IL-1 β could increase the availability of L-arginine for NO synthases in CF airways.

“The strong relation of IL-1β with FeNO and L-arginine/ADMA, a ratio that is reduced in CF and that can be used to quantify [nitric oxide synthase] impairment, could provide a potential mechanism as to how FeNO increases through CFTR modulator therapy,” the authors said.

Moreover, the authors found correlations between the levels of IL-1β and IL-1α, IL-1RA, IL-8, and IL-17a, but not with IL-6. Also, IL-1α levels were correlated with IL-1RA and IL-17a levels, but not with IL-6 or IL-8 levels. IL-1 signaling pathway has been associated with early mucus hypersecretion, inflammation, and CFTR dysfunction in CF.


Nissen G, Ben-Meir E, Kopp M, Shaw M, Ratjen F, Grasemann H. Interleukin-1 beta is a potential mediator of airway nitric oxide deficiency in cystic fibrosis. J Cyst Fibros. Published online March 5, 2022. doi:10.1016/j.jcf.2022.02.017