Asthma and lower airway diseaseIL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers
Section snippets
Volunteer recruitment and inclusion criteria
This protocol was reviewed and approved by the University of North Carolina (UNC) Committee on the Rights of Human Subjects (Institutional Review Board) and by the Data and Safety Monitoring Board of the National Institute of Allergy and Infectious Diseases (AADCRC-UNC-03). This study was also reported to and reviewed by the US Food and Drug Administration (IND 14,669) and listed on clinicaltrials.gov as NCT01369017.
This was a double-blind, placebo-controlled crossover study comparing the
Subjects' demographics and adverse events
Twenty-three healthy volunteers were enrolled. Six subjects were excluded after failing the induced sputum screening. Seventeen subjects successfully completed period 1, and 15 subjects completed the entire study (Table I). Eight subjects received active treatment during period 1, and 9 subjects received placebo treatment during period 1.
Two subjects were withdrawn after period 1 because of study-related adverse events. Subject 10 experienced injection-site reactions 1 week after period 1
Discussion
The purpose of this early-phase human study was to determine whether in vivo treatment with anakinra could be a safe and effective intervention in an acute model of neutrophilic airway inflammation induced by LPS inhalation. In healthy volunteers we found that anakinra treatment decreased LPS-induced percentage neutrophils in sputum by 80%. Furthermore, this treatment was well tolerated by our healthy volunteer population.
Although anakinra treatment affected IL-1ra levels in the blood, it did
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M.L.H. is supported by National Institute of Environmental Health Sciences grant K23-ES021745. K.M., M.A., H.Z., H.Z., and D.B.P. are supported by National Institute of Allergy and Infectious Diseases grant U19AI077437.
Disclosure of potential conflict of interest: This study was funded by a grant from the National Institute of Allergy and Infectious Diseases (U19AI077437). The authors declare that they have no other relevant conflicts of interest.