Effect of oxygen status on innate immune functions in human endotoxemia
Kiers, H.D., John, J., Janssen, E., Scheffer, G.J., Hoeven, J.G. van der, Pickkers, P., Kox, M.
Voorzitter(s): dr. B.J. Looij, Geleen & dr. Y.W.J. Sijpkens, Den Haag
Locatie(s): Zaal 2.1
Categorie(ën):
Introduction: Preclinical studies have shown that hypoxia and hyperoxia influence the innate immune response. In vitro, hypoxia has been shown to exert pro-inflammatory effects, supposedly mediated by the transcription factor hypoxia inducible factor 1α (HIF1α), whereas hyperoxia is related to immune suppression. Therefore, hypoxia and hyperoxia could be cheap, non-pharmacological, non-invasive treatment modalities to modulate inflammatory conditions. However, the effects in humans in vivo have hitherto not been investigated.
The aim of this study: To evaluate the effects of hypoxia and hyperoxia on the innate immune response during experimental endotoxemia in healthy volunteers.
Methods: 30 healthy, male volunteers were randomized to hypoxia, normoxia or hyperoxia (n=10 per group). Subjects were exposed to a total of 3,5 hours of hypoxia (arterial oxygen saturation 80-85%), normoxia or hyperoxia (fraction of inspired oxygen >95%). 1 hour into oxygen status adjustment, a bolus injection of 2 ng/kg purified E. coli endotoxin was administered to induce systemic inflammation. Saturation, hemodynamics, blood gas analysis, leukocyte differentiation , circulating cytokines and intracellular HIF-1α expression in neutrophils, monocytes and lymphocytes were determined.
Results: Hypoxia (SaO2 81.9(± 0.5)%) was induced using an FiO2 of 11.5 (±0.8)%. Hyperoxia (FiO2 97.9(±0.2) %) resulted in a mean PaO2 of 54.1 (±4.1) kPa. Endotoxemia induced neutrocytosis and resulted in a transient monocytopenia. Hypoxia potentiated the increase in neutrophils and also increased monocyte number (P<0.0001), whereas hyperoxia did not affect leukocyte counts(p=0.44). Endotoxin administration resulted in increase in all measured plasma cytokines. Hypoxia attenuated endotoxin-induced plasma pro-inflammatory cytokines TNFα, IL-6 and IL-8 (p<0.0001) and potentiated anti-inflammatory IL-10 production (p=0.001). Hyperoxia did not alter endotoxemia induced cytokines. HIF-1α expression was increased in circulating neutrophils 2,5 and 6 hours after endotoxin administration, and after 6 hours in circulating lymphocytes in all three groups but hypoxia or hyperoxia did not affect HIF-1α expression.
Conclusion: Hypoxia in healthy humans attenuates endotoxin-induced systemic inflammation, whereas hyperoxia does not affect this response. Endotoxemia increases HIF-1α in neutrophils and lymphocytes independent of oxygen status.
- Over Kiers, H.D.
- Over John, J.
- Over Janssen, E.
- Over Scheffer, G.J.
- Over Hoeven, J.G. van der
- Over Pickkers, P.
- Over Kox, M.