Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men - Serebrovskaya et al. (2011)

Key Points

  • Intermittent hypoxia (IH) improves innate immune function and enhances body’s ability to fight infection

  • IH has a net anti-inflammatory effect

  • IH has potential application in immunotherapy

The Breathing Diabetic Summary

From the title, I would have never guessed how important this paper is. I basically underlined and wrote “WOW” next to every paragraph! Overall, the authors show that intermittent hypoxia enhances the innate immune system, is anti-inflammatory, and activates a specific type of stem cells that generate all blood cells. Some of these findings also support the incredible immune responses seen in practitioners of the Wim Hof Method.

We know from the 2014 review study that the effects of IH are dose dependent, and that there is a big difference between chronic IH and moderate IH.  This paper uses a moderate IH protocol and they implement it over a 2-week period.  They also tested the impacts of one single bout of IH on different markers to test the difference between longer-term practice of IH (2 weeks) or one single session.  The long-term group dropped blood oxygen saturation to 84-85% for 5 min and completed 4 cycles of this every day for 14 days.  The short-term group simply completed 4 cycles of IH one day.

 We also know from the 2014 review study that IH helps many different bodily functions, however, this study presents interesting previous research on how IH might promote stem cell proliferation.  They note that previous studies have not examined the effects of different IH protocols on stem cells, which is the goal of their research.  However, they also looked at several markers of inflammation and immune function and found some fascinating results.

First, they found that IH reduced the concentration of proinflammatory cytokines.  This same suppression of proinflammatory cytokines occurred in the PNAS Wim Hof study.  However, here, we see the suppression without breath-holding and in a scenario where easily tolerated the hypoxia by simply breathing air with reduced oxygen content.  Thus, it appears that the cycles of IH used in the Wim Hof Method might be the critical component triggering this anti-inflammatory immune response.  They also found that a single session of IH elicited positive changes on inflammatory and immune markers, similar to that of the long-term practice.

One very interesting results was that IH activated the body’s “complement system,” a part of the immune system that enhances the ability of antibodies. A recent study highlights the importance of proteins that are part of the complement system to diabetes: “One protein, CD59, was shown to be essential for enabling beta cells to secrete insulin.” This is definitely something worth looking into further.

In the discussion of their results, the authors point out that the immune response triggered by IH might be especially important for fighting infections.  As diabetics, we know that we are more susceptible to infections (e.g., pneumonia), so using breath holds to experience IH (Principle 3) might be a way to enhance our already compromised immune systems. (Note: Anytime I feel a cold coming on, I practice extra breath holds to elicit the response noted here. It always seems to help fight off the cold, or at least reduce the severity. I used to think it was just a placebo effect, but after reading this paper I see that there are many scientifically proven mechanisms at work.)

Overall, this study found that IH improves immunity (with specific improvements that enhance the body’s ability combat infection), increases complement activity, and has a net anti-inflammatory effect.  These results could be extremely important to diabetics since we have compromised immune systems, have reduced insulin secretion (type 2) that could be enhanced by increased complement, and suffer from higher levels of inflammation due to fluctuating blood sugars.

Abstract From Paper

Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men. High Alt. Med. Biol.  12:243 252.—This study tested the hypothesis that intermittent hypoxia treatment (IHT) modulates circulating hematopoietic stem and progenitor cells (HSPC) and augments humoral and cellular components of innate immunity in young, healthy men. Ten subjects (group 1: age 31 –  4 yr) were studied before and at 1 and 7 days after a 14-day IHT program consisting of four 5-min bouts/day of breathing 10% O2, lowering arterial O2  saturation to 84% to 85%, with intervening 5-min room air exposures. Five more subjects (group 2: age 29 –  5 yr) were studied during 1 IHT session. Immunofluorescence detected HSPCs as CD45+ CD34+  cells in peripheral blood. Phagocytic and bactericidal activities of neutrophils, circulating immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines (erythropoietin, TNF-a , IL-4, IFN-c ) were measured. In group 1, the HSPC count fell 27% below pre-IHT baseline 1 week after completing IHT, without altering erythrocyte and reticulocyte counts. The IHT program also activated complement, increased circulating platelets, augmented phagocytic and bactericidal activities of neutrophils, sharply lowered circulating TNF-a  and IL-4 by >  90% and * 75%, respectively, and increased IFN-c , particularly 1 week after IHT. During acute IHT (group 2), HSPC increased by 51% after the second hypoxia bout and by 19% after the fourth bout, and total leukocyte, neutrophil, monocyte, and lymphocyte counts also increased; but these effects subsided by 30 min post-IHT. Collectively, these results demonstrate that IHT enhances innate immunity by mobilizing HSPC, activating neutrophils, and increasing circulating complement and immunoglobulins. These findings support the potential for eventual application of IHT for immunotherapy.

Journal Reference:

 Tatiana V. Serebrovskaya, Igor S. Nikolsky, Valentyna V. Nikolska, Robert T. Mallet, and Vadim A. Ishchuk, (2011) Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men, High Altitude Medicine & Biology, 12 (3), DOI:10.1089/ham.2010.1086.