The Cogence Clinical Pearls Series

Anemia, Poor Circulation, Respiratory Problems Can All Increase Vulnerability to Infection

What the research says…

This paper, from Immunology Letters, demonstrates that natural killer cells, a key inhibitor of viruses and other pathogens in the body, differentiate along an oxygen gradient. This links marginal O2 status with marginal NK cell function in a crucial way, providing a key clinical insight in the management of patients with both autoimmunity and chronic infectious burden.

Application…

Many of our most difficult patients have both autoimmunity and chronic infection. Low NK cell levels are a crucial marker in working with autoimmune and chronically infected patients. So many patients have NK cell levels in the lowest 20% of the normal range, despite carrying chronically elevated pathogen burdens that should be promoting much more robust NK cell responses. This is crucial, because viruses are known to drive the initiation of new autoimmune processes. It’s also well established that patients with existing autoimmune disease are at greater risk for developing another target of immune system attack. In other words, patients with one autoimmune disease are more likely to get another autoimmune disease. For these people especially, it’s important they not carry a larger burden of viral pathogens. But, if their NK cells aren’t differentiating efficiently, they may not be able to keep their viral burden down.

So, if you have a patient with autoimmunity, ask yourself, “Does this autoimmune patient also have anemia, circulatory issues, or respiratory issues?” If so, it’s crucial to address these sources of low oxygen. It’s very common to see patients who either have anemia, suboptimal SpO2 (below 96%) or poor circulatory perfusion. If you can restore more abundant oxygen, you’ll really help the patient keep their viral burdens low. And, because higher viral burdens are associated with greater systemic inflammation, keeping the burden lower will also help to reduce systemic inflammation.

Research…

Oxygen tension regulates NK cells differentiation from hematopoietic stem cells in vitro.
Immunol Lett. 2011 Jun 30;137(1-2):70-7. Yun S, Lee SH, Yoon SR, Myung PK, Choi I.

(Color and bold added.)
Abstract

Natural killer (NK) cells are differentiated from hematopoietic stem cells (HSCs) which are located at the lowest end of an oxygen gradient within the bone marrow (BM). In this report, we investigated whether oxygen tension could affect NK cell differentiation from hematopoietic cells in vitro. We found that hypoxia led to an inhibition of differentiation in NK cells, and increased oxygen supply alleviated this inhibition and restored NK cell differentiation under hypoxic condition. Hypoxia-treated cells demonstrated reduced mRNA expression of transcription factors (TFs) that have important roles in NK cell differentiation, such as EOMES, T-bet, GATA-3 and ETS-1. Moreover, hypoxia-pretreated cells recovered mRNA expression of TFs when the oxygen tension was changed to normoxia. Our findings suggest that oxygen tension modulates in vitro differentiation of NK cells through the regulation of TF expression.