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.