RT Journal Article
SR Electronic
T1 Rational drug design for sore throat—An aspirin-based treatment that addresses bradykinin-induced inflammation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.06.370395
DO 10.1101/2020.11.06.370395
A1 Victor Leyva-Grado
A1 Pavel Pugach
A1 Nazlie Latefi
YR 2020
UL http://biorxiv.org/content/early/2020/11/08/2020.11.06.370395.abstract
AB Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic prescriptions. Despite being on the market for decades, few over the counter sore throat medications are proven to heal sore throat. In studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in prostaglandin E2 (PGE2) and interleukin-8 (IL-8) in response to bradykinin. Bradykinin is one of the first inflammatory signals for pharyngitis and it increases PGE2 in human subjects. If left unregulated, PGE2 may further increase inflammation via the COX pathway and via IL-8, a proinflammatory chemokine responsible for neutrophil infiltration and possibly thus, a cytokine storm. Acetyl salicylic acid (ASA), a non-specific COX inhibitor, was able to mitigate a bradykinin-induced increase in PGE2 in our studies. However, ASA was inflammatory above its small therapeutic window, greatly increasing levels of PGE2 and IL-8 above those seen with bradykinin stimulation alone. Similar to other systems, the respiratory epithelia maintains a delicate balance of pro-inflammatory and anti-inflammatory signals in order to keep the respiratory barrier intact. To our knowledge, this is the first study to try and elucidate the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the respiratory epithelia. Biovanta™, a formula containing ASA mitigated bradykinin-induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL-8 in organotypic human respiratory tissues, suggesting these common treatments may possibly increase the likelihood of further respiratory complications in people.Competing Interest StatementThis study was funded entirely by Applied Biological Laboratories, a private company that owns the BiovantaTM product. Unless otherwise indicated all experiments were performed at Applied Biological Laboratories research facility located at the SUNY Downstate Biotechnology Incubator, a part of StartUP NY. All of the authors were employees of Applied Biological Laboratories at the time the experiments were performed.