Treatment with 7% and 10% CO2 enhanced expression of IL-1β, TNF-α, and IL-6 in hypoxic cultures of human whole blood

Objective: This study investigated whether hypercapnia influenced the inflammatory response of hypoxic blood.

Methods: Human whole blood was cultured with 0.2% oxygen (O₂) and treated with 5%, 7%, or 10% carbon dioxide (CO₂). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were evaluated in whole blood cultures. Reactive Oxygen Species (ROS) production and expression levels of Caspase-1 and IL-1β were evaluated in THP-1 monocytic cells.

Results: IL-1β, TNF-α, and IL-6 levels were higher in the hypoxia + 7% CO₂ group than in the hypoxia + 5% CO₂ group. The hypoxia + 10% CO₂ group had the highest IL-1β, TNF-α, and IL-6 levels, compared with the hypoxia + 7% CO₂ and hypoxia + 5% CO₂ groups. Expression levels of IL-1β, TNF-α, and IL-6 were significantly negatively correlated with pH levels in the Cell Culture medium. Treatment with 7% and 10% CO₂ increased the production of ROS and the expression of Caspase-1 and IL-1β in hypoxia-activated THP-1 cells.

Conclusions: High levels of CO₂ treatment increased expression levels of IL-1β, TNF-α, and IL-6 in hypoxic whole blood cultures. High levels of CO₂-induced ROS overproduction and NLRP3 inflammasome activation in monocytes may comprise a target to mitigate the inflammatory response of hypoxic blood.