Simon Blaine-Sauer

Objectives 17β‐estradiol (E2) is a steroidal hormone with immunomodulatory functions that play a role in infectious and inflammatory diseases. E2 was recently identified as the leading upstream regulator of differentially expressed genes in a comparative RNA sequencing study of pediatric patients with otitis media (OM) versus OM‐free counterparts and may therefore play a role in the inflammatory response to bacterial otopathogens during pediatric OM. This study examined the effect of E2 on bacterial‐induced inflammatory cytokine expression in an in vitro pediatric OM model. Methods An immortalized middle ear (ME) epithelial cell line, ROM‐SV40, was developed from a pediatric recurrent OM patient. The culture was exposed to E2 at physiological levels for 1–48 h prior to 6 h‐stimulation with nontypeable Haemophilus influenzae (NTHi) whole cell lysate. TNFA , IL1B , IL6 , and IL8 were assayed by qPCR and ELISA. Results E2 pretreatment (24 h) abrogated NTHi induction of IL6 ; a longer pretreatment (1–10 nM, 48 h) abrogated IL1B induction ( p < 0.05). E2 pretreatment (5 nM, 48 h) abrogated NTHi‐induced IL8 secretion ( p = 0.017). Conclusion E2 pretreatment partially rescued NTHi‐induced cytokine production by ME epithelia. These data support a role for E2 in moderating the excessive inflammatory response to middle ear infection that contributes to OM pathophysiology. Levels of Evidence NA Laryngoscope , 2024

Objective Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. Methods Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. Results Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. Conclusion Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. Level of Evidence NA Laryngoscope , 134:2322–2330, 2024