J Biol Regul Homeost Agents. May-Jun 2021; 35(3):901-908. doi: 10.23812/21-35-3-E2.


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Neurohormonal markers in chronic rhinosinusitis

Compton RA1, Lonergan AR2, Tsillioni I3, Conti P4, Ronconi G5, Lauritano D6, Rebeiz EE7, Theoharides TC3,8.

Author information

1  Department of Otolaryngology, Tufts Medical Center, Boston, MA, USA.
2  Department of Otolaryngology, University of California Irvine, Orange, CA, USA.
3  Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA, USA.
4  Postgraduate Medical School, University of Chieti, Pescara, Italy.
5  Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, Rome, Italy.
6  University of Milan-Bicocca, Medicine and Surgery Department, Centre of Neuroscience of Milan, Italy.
7  †Deceased / Department of Otolaryngology, Tufts Medical Center, Boston, MA, USA.
8  School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.


Chronic rhinosinusitis (CRS), especially with nasal polyps, continues to elude precise pathogenesis and effective treatment. Prior work in our laboratory demonstrated interleukin-33 (IL-33) and Substance P (SP) activation of mast cells, and inhibitory effect of interleukin-37 (IL-37). Our objective is to study the expression of these neurohormonal mediators in mast cell stimulation of nasal polyposis. This was a prospective research study involving collection of nasal lavage fluid and nasal polyp tissue from adult patients with CRS. The study was divided into two arms. First, nasal lavage fluid was collected from normal controls, and patients with allergic rhinitis, CRS, or CRS with nasal polyposis. The second arm was collection of nasal tissue from normal controls undergoing inferior turbinoplasty, or patients with nasal polyposis. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction techniques were used to determine levels in the lavage fluid and relative gene expression in the tissue of SP, IL-33, and IL-37. In total, 70 lavage and 23 tissue specimens were obtained. The level of SP was highest in patients with polyps; however, gene expression was reduced compared to normal controls. The level of IL-33 was reduced in patients with polyps as compared to patients with allergy and sinusitis, and its gene expression was not significantly different from normal controls. IL-37 was elevated in the lavage fluid of patients with nasal polyps and its gene expression was increased in the polyp tissue. Levels of SP and IL-37 were elevated in the lavage fluid of patients with nasal polyps as compared to normal controls and other sinonasal pathologies, and gene expression of IL-37 was significantly increased in the polyp tissue itself. These findings implicate these neurohormonal molecules in the pathophysiology of nasal polyposis and provide possible novel therapeutic targets.


chronic sinusitis, inflammation, interleukin-33, interleukin-37, mast cells, nasal polyps, substance P

Publication type

  • Journal Article

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