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APPA modulates pathological aspects of human neutrophil function, without suppressing antimicrobial ability, and inhibits TNFα expression and signalling

A greater understanding of neutrophil biology has led to an appreciation that these cells play a significant role in many systemic inflammatory conditions but targeting neutrophils therapeutically has proven challenging, as host defences must not be compromised. Neutrophils contribute to inflammatory diseases via the release of cytokines, chemokines, reactive oxygen species (ROS) and proteases. Successful targeting of neutrophils as a therapy in inflammatory diseases must therefore block tissue-damaging processes (e.g. release of cytokines) but not interfere with host defence mechanisms

This report confirms that APPA significantly down-regulates TNFα-mediated expression of cytokines and chemokines by neutrophils. Importantly it also confirms that APPA does not interfere with host defence neutrophil functions such as receptor expression, phagocytosis and bacterial killing

This suggests that APPA may have significant anti-inflammatory potential in diseases characterised by dysregulation of cytokine expression or oxidative stress, not only in Osteoarthritis, for which the drug is currently being developed, but also in systemic inflammatory diseases such as Rheumatoid Arthritis without suppressing host defences

Full Publication:           https://doi.org/10.1007/s10787-020-00715-5

Cross AL, Hawkes J, Wright HL, Moots RJ, Edwards SW. APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, without supressing antimicrobial ability, and inhibits TNFα expression and signalling. Inflammopharmacology. 2020;10.1007/s10787-020-00715-5