Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)

• Published in: Scientific reports Vol. 11; no. 1; pp. 8054 - 11
• Main Authors: Wang, Yi-Jun, Monteagudo, Alina, Downey, Matthew A., Ashton-Rickardt, Philip G., Elmaleh, David R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/127; 631/250/2504/342/1952; 631/250/256; 631/250/371; 631/250/98; 692/699/375/132; 692/699/375/364; 692/699/375/365; 692/699/375/365/1283; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Asthma; CCL3 protein; CCL4 protein; Cell Line; Chemokines; Chemokines - metabolism; Cromolyn Sodium - pharmacology; CXCL10 protein; Cytokines; Cytokines - metabolism; Dosage; Humanities and Social Sciences; Humans; Ibuprofen; IL-1β; Inflammation; Inflammation Mediators - metabolism; Interleukin 6; Interleukin 8; Microglia; Microglia - drug effects; Microglia - metabolism; Monocyte chemoattractant protein 1; multidisciplinary; Neurodegenerative diseases; Science; Science (multidisciplinary); Tumor necrosis factor-α; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85702-8

Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer’s Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.