Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback. Asthma: Unveiling the molecular effects of aspirin Researchers in Korea have revealed how acetyl salicylic acid (ASA), or aspirin, soothes airway inflammation, such as that caused by asthma. Yoon-Keun Kim of the Pohang University of Science and Technology (POSTECH) and his team used a mouse model of asthma to show how ASA ameliorates swelling and narrowing of the airways. Often touted as an anti-inflammatory ‘wonder drug’, ASA acts through multiple mechanisms. Kim and colleagues' study revealed that ASA suppresses a subset of immune cells, called Th17 cells, by indirectly blocking the production of the signaling molecule interleukin (IL)-6. ASA inhibits the production of IL-17A, which normally enhances IL-6 production. However, ASA is not effective against Th1 cells, which are closely related to Th17 cells and also contribute to asthma.