No abstract

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by the environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas. FDA-approved drug library screen identified pitavastatin as an effective IL-33 inhibitor by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevented chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. IRF3-IL-33 axis was highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlated with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3 signaling pathway suppresses IL-33 expression and cancer-prone chronic inflammation. Statins present a safe and effective therapeutic strategy to prevent chronic inflammation and its cancer sequela.

Purpose: We evaluated the ability of muscle ultrasound (MUS), a non-invasive and simple tool, to distinguish between healthy subjects and individuals with inflammatory myopathy. Methods: This study was conducted on 17 patients with recently diagnosed biopsy-proven inflammatory myopathies (12 dermatomyositis, five polymyositis) compared with 17 age- and gender-matched healthy control adults. All patients underwent clinical assessments, including manual muscle testing (MMT) and hand-held dynamometry, as well as MUS evaluations, including thickness and echointensity (EI) in predefined muscle groups. Results: The disease duration was seven months (interquartile range: 3-11). Except for biceps and gastrocnemius, the patients' muscles had significantly higher EI and lower thickness in comparison with the controls, The EI sum-score manifested the highest area under curve (AUC) in comparison with the sum-scores of other variables (EI vs. MMT: AUCs-difference = 0.18, p < 0.01; EI vs. dynamometry: AUCs-difference = 0.14, p = 0.02; EI vs. thickness: AUCs-difference = 0.25, p < 0.01). Conclusion: EI of muscles differed significantly between healthy individuals and those with inflammatory myopathies and may potentially serve as a useful diagnostic biomarker.