Figure 1

Modulating effect of hypercapnic acidosis on the inflammatory response. NF-κB can be activated by multiple stimuli, such as endotoxin (lipopolysaccharide), reactive oxygen species (ROS) and cytokines (IL-1β and TNF-α). Subsequently, phosphorylation of IκB (inhibitory proteins κB) occurs followed by its degradation, allowing NF-κB to be transported to the cell nucleus where it binds to specific promoter sites and activates transcription of target genes. Following activation of NF-κB, both intra- and extracellular feedback mechanism will subsequently regulate NF-κB activation, with IL-1β and TNF-α providing positive extracellular feedback. The potential mechanism by which hypercapnic acidosis (HCA) inhibits NF-κB activation appears to involve suppression of the degradation of IκB-α. Subsequently, this will result in suppressed production of IL-1β, IL-6, IL-8 and TNF-α. Suppression of intercellular adhesion molecule (ICAM)-1 and IL-8 will subsequently lead to inhibition of neutrophil adherence. HCA may also offer protection against ROS-mediated lung injury by inhibiting xanthine oxidase (XO).