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\begin{document}

\title{Ivacaftor alters macrophage and lymphocyte infiltration in the lung
following lipopolysaccharide exposure}



\author[1]{Kiera Harwood}%
\author[1]{Rachel McQuade}%
\author[2]{Andrew Jarnicki}%
\author[1]{Elena Schneider-Futschik}%
\affil[1]{The University of Melbourne}%
\affil[2]{University of Newcastle}%


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  \date{May 24, 2024}


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\begin{abstract}
Background and Purpose: Cystic fibrosis (CF) is associated with a myriad
of respiratory complications including increased susceptibility to lung
infections and inflammation. Progressive inflammatory insults lead to
airway damage and remodelling, resulting in compromised lung function.
Treatment with ivacaftor significantly improves respiratory function and
reduces the incidence of pulmonary exacerbations; however, its effect on
lung inflammation is yet to be fully elucidated. Experimental approach:
This study investigates the anti-inflammatory effects of ivacaftor in
the lung post lipopolysaccharide (LPS) exposure and compare effects of
prophylactic and therapeutic ivacaftor treatment in a C57BL/6 mice
model. All groups received intratracheal (IT) administration of LPS (10
ug). Prophylactic treatment involved intraperitoneal injections of
ivacaftor (40mg/kg) once a day beginning 4 days prior to LPS challenge.
The therapeutic group received a single intraperitoneal ivacaftor
injection (40mg/kg) directly after LPS. Mice were culled either 24h or
72h post LPS challenge and serum, bronchoalveolar lavage fluid (BALF)
and lung tissue samples were collected. The degree of inflammation was
assessed through cell infiltration, cytokine expression and histological
analysis. Key Results: Ivacaftor did not alter the total number of
immune cells within the BALF, however, prophylactic treatment did
significantly alter macrophage and lymphocyte infiltration. Prophylactic
treatment saw a significant negative correlation between immune cell
number and ivacaftor concentrations in BALF, however, no significant
changes in cytokine expression nor histological parameters were
determined. Conclusion \& Implications: Ivacaftor possesses some
inherent immunomodulatory effects within the lung following LPS
inoculation, however, further analysis of larger sample sizes is
required to confirm results.%
\end{abstract}%



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