Novel immunomodulatory agents are being developed to treat the inflammatory signaling molecules that trigger eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), according to study results presented at the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) 2022 Annual Meeting and OTO Experience, held from September 10 to 14, 2022, in Philadelphia, Pennsylvania.
Researchers conducted a study in which they sought to establish the effect of
5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on thymic stromal lymphopoietin (TSLP) and eotaxin-3, which play important roles in the pathogenesis of CRSwNP.
An adenosine monophosphate-activated protein kinase (AMPK) agonist, AICAR exhibits anti-inflammatory properties on TSLP and eotaxin-3 production in nasal polyp epithelial cells. Advances in understanding the inflammatory signaling molecules implicated in patients with CRSwNP have paved the way for the use of novel immunomodulating agents such as AICAR for the treatment of this refractory disorder.
Nasal polyps from 5 patients with eosinophilic CRSwNP were obtained at the time of surgery. All of the epithelial cells were isolated and expanded with the use of cell culture protocols. For induction of TSLP production, the epithelial cells were treated with the toll-like receptor 3 agonist poly (I:C) and the Th2 cytokine interleukin-4 (IL-4). For induction of eotaxin-3 production, the epithelial cells were treated with IL-4 alone. All of the cells were pretreated with either AICAR or vehicle control. Quantitative polymerase chain reaction and enzyme-immunosorbent assays were used to evaluate the quantitative differences in mRNA production and protein secretion.
Pretreatment of nasal polyp epithelial cells with AICAR was associated with a 60% decrease in secreted TSLP protein and an 83% TSLP mRNA fold change decrease (P =.0461 and P <.0001, respectively). Similarly, pretreatment of the nasal polyp epithelial cells with AICAR was associated with an 80% decrease in secreted eotaxin-3 protein and an 82% eotaxin-3 mRNA fold change decrease (P =.0053 and P =.0001, respectively).
The researchers concluded, “[Additional] research is warranted to further explore the mechanism and additional effects of AICAR and other AMPK agonists on CRSwNP inflammation and [to] evaluate their potential use as topical or systemic therapies for this often refractory disease.”
Sylvester MJ, Fattahi F, Ellis J, Zacharek MA, Atasoy U. AICAR inhibits thymic stromal lymphopoietin and eotaxin-3 production in eosinophilic nasal polyp epithelium. Otolaryngol Head Neck Surg. 2022;167(1 suppl):P280.