Elio Rossi (@eliorossi.bsky.social)

Clinical implications of innate immune exhaustion in cystic fibrosis Objectives The lung disease progression in people with cystic fibrosis (pwCF) varies from one individual to another. Different immunological characteristics have been suggested to explain this variation, and we hypothesized that lung capacity may be associated with the innate immune response in pwCF. In an exploratory study, we aimed to investigate potential links between the innate immune response and lung function in pwCF using the standardized immune function assay TruCulture. Methods In a single-centre study with combined cross-sectional and longitudinal data before and after intravenous antibiotics, blood was sampled from Pseudomonas aeruginosa infected pwCF. Whole blood was analysed by TruCulture to reveal the unstimulated and stimulated cytokine release. Tobit regressions and Spearman's correlations were used to estimate the associations between lung function and cytokine release. Results We included 52 pwCF in the cross-sectional study and 24 in the longitudinal study. In the cross-sectional study, we found that compared to a healthy population the release of toll-like receptor (TLR)3, −4 and −7/8 stimulated IFN-γ, and IL-12p40 were reduced. Although TLR3-stimulated IL-1β and IL-6 release increased with lung function, overall, cytokine release did not correlate well with lung function. In the longitudinal study, the cytokine release was modified by antibiotic treatment, but the cytokine release before antibiotic treatment did not associate with changes in lung function after treatment. Conclusion The stimulated cytokine release could not predict lung function levels or changes in pwCF, but our data indicate that pwCF experience exhaustion in the innate immune response after years of chronic bacterial infection. Footnotes This manuscript has recently been accepted for publication in the ERJ Open Research . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article. Conflict of interest: Sisse Rye Ostrowski has nothing to disclose. Conflict of interest: Tacjana Pressler has nothing to disclose. Conflict of interest: Helle Krogh Johansen has nothing to disclose. Conflict of interest: Elio Rossi discloses Biomedical research conducted by young researchers grant (2020-3581), payment to Università degli Studi di Milanoor contracts from Cariplo Foundation, disclosure made outside the submitted work. Conflict of interest: Rikke Møller has nothing to disclose. Conflict of interest: Bibi Uhre Nielsen has nothing to disclose. Conflict of interest: Mads Lausen has nothing to disclose. Conflict of interest: Marianne Skov has nothing to disclose. https://openres.ersjournals.com/content/early/2024/04/11/23120541.00256-2024