2.1.1Inflammatory factors
Numerous studies have confirmed the increased expression levels of pro-inflammatory factors in children with BPD, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α40-42.In vitro experiments showed that caffeine reduced IL-1β and IL-18 secretion in lipopolysaccharide (LPS)-induced THP-1 macrophages43.In animal experiments involving hyperoxia-induced lung injury, it was confirmed that caffeine treatment not only reduced the expression of cyclooxygenase(COX-2),myeloperoxidase(MPO), TNF-α, and IL-1β44,but also reduced leukocyte infiltration and decreased the release of pro-inflammatory factors and chemokines in the lungs, thus protecting against hyperoxia-induced alveolar dysplasia45.In a young rat model of LPS-induced pro-inflammatory amnionitis, caffeine exerted anti-inflammatory effects and improved lung function by inhibiting the expression of IL-1β and CD6846. In a cohort study of preterm infants, Raul et al.found that BPD was associated with higher concentrations of IL-1 and IL-6, a greater imbalance between these cytokines and IL-10, and that alterations occurred in tracheal secretions and peripheral blood inflammatory factors before and after caffeine administration47.At therapeutic levels of 10-20 mg/mL, caffeine prevented the sustained activation of the inflammatory cascade response, although serum caffeine levels >20 mg/mL resulted in elevated levels of IL-1b, IL-6,but TNF-a and decreased IL-10 concentrations. Thus, in vitro and in vivo experiments , together with clinical trials, have shown that caffeine reduces to lung injury by modulating changes in inflammatory factors.