Hyperoxia stimulates interleukin-8 release from alveolar macrophages and U937 cells: attenuation by dexamethasone

Abstract

Pulmonary oxygen toxicity is associated with histological evidence of polymorphonuclear neutrophil (PMN) infiltration into lung parenchyma. What guides infiltration of these cells is unknown. A number of chemoattractants for PMN have been documented including interleukin-8 (IL-8), a cytokine released by alveolar macrophages (AM) and other cell types. The purposes of this study were to 1) determine whether human AM and the histiocytic U937 cell line release IL-8 in response to hyperoxia, 2) assess whether hyperoxia results in increased IL-8 steady-state mRNA levels in U937 cells and 3) establish whether dexamethasone could attenuate noted effects of hyperoxia. Our study shows that hyperoxia stimulates human AM and U937 cell release of IL-8. Hyperoxia also increases IL-8 mRNA levels in U937 cells. IL-8 released in response to hyperoxia by AM was biologically active as evidenced by ability to induce PMN chemotaxis. A polyclonal antibody to IL-8 partially attenuated this chemotactic activity. Finally, dexamethasone at concentrations of 10 microM, 1 microM, and 100 nM markedly reduced hyperoxia-induced IL-8 release and mRNA synthesis by U937 cells. We conclude that IL-8 may be important in the pathogenesis of pulmonary oxygen toxicity and that therapeutic concentrations of dexamethasone can suppress production of this cytokine.

Human recombinant apyrase therapy protects against canine pulmonary ischemia-reperfusion injury

“…Also, the use of steroids in our model makes it more difficult to discern the direct effects of apyrase on lung inflammation. For example, its well-accepted that steroids inhibit inflammatory cytokine production by macrophages 32, 33 but they may also worsen pulmonary neutrophilia as dexamethasone is reported to enhance eATP-mediated endothelial cell expression of adhesion molecules and IL-8 34 . Additionally, we did not obtain pre-transplant BALF samples from donors or recipients where data on eATP levels may have been informative to better assess the impact of pre-existing pathologies on the release of this DAMP following engraftment.…”

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

“…26 When the inhaled O 2 exceeds the protective capacity of antioxidants present in the lungs, acute pulmonary pneumonitis associated with the release of proinflammatory cytokines by alveolar macrophages, specifically IL-8 and IL-6, develops. 10,11 The amount of these proinflammatory cytokines in the BAL is associated with acute lung injury and pulmonary infection similar to acute respiratory distress syndrome. 15,36 In the combined HBO 2 /NBH group, patients' BAL levels of IL-6 and IL-8 cytokines did not significantly differ posttreatment from the control group levels.…”

Effect of Hyperoxia on Vascular Endothelial Growth Factor Levels in a Wound Model

“…Cell culture data suggest that hyperoxia may well change the concentration and receptor density of other wound-active growth factors. 12,[14][15][16] If VEGF concentration directly responds to hyperoxia, it is possible that other growth factors respond similarly and potentiate angiogenesis. Undoubtedly, more aspects of hyperoxia remain to be discovered.…”

“…12,13 In addition, macrophages and endothelial cells that are exposed to hyperoxia up-regulate IL-8, transforming growth factor ␤, and VEGF messenger RNA. [14][15][16] The possibility arises, therefore, that hyperoxia may actually induce VEGF production in wounds.…”