Re: "Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness,Physiological Variables,or Cytokine Levels" by Lundeberg,et al. (High Alt Med Biol 2018 19:249–258)

Lundeberg et al. (2018) recently reported on the effects of ibuprofen treatment on cytokine levels and the development of acute mountain sickness (AMS) when acutely exposed to high altitude (3800 m). I read with interest the exiting outcomes of this comprehensive investigation. However, in my opinion, the rationale for this study and the presented conclusions are not really convincing. The authors assumed that ibuprofen would block the hypoxia-induced elevation of inflammatory cytokine levels and consequently inhibit ventilatory acclimatization. This assumption is based on a single animal study demonstrating reduced increases of cytokines with ibuprofen in the brainstem of rats exposed to chronic hypoxia (Popa et al., 2011). In this article, no mechanisms are provided for the expected interaction between ibuprofen and cytokine synthesis (Lundeberg et al., 2018). Human studies rather indicate an increase in cytokine levels with the use of nonsteroidal anti-inflammatory drugs (Endres et al., 1996). Inhibitors of cyclo-oxygenase diminish prostaglandin E2 levels and associated symptoms, but may not reduce cytokine levels (Endres et al., 1996), which has also been confirmed in this study (Lundeberg et al., 2018). Furthermore, I do not agree with the conclusion that AMS development is not affected by ibuprofen. In my opinion, figure 1 clearly indicates beneficial effect on the total AMS score and some AMS symptoms at arrival and after 12 hours at altitude (Lundeberg et al., 2018). In fact, this would have been expected based on several studies demonstrating favorable prevention and treatment effects on AMS by cyclo-oxygenase inhibition (Burtscher et al., 1998; Gertsch et al., 2010).