Natural killer cells – Canaries in the immunological coal mine

NeuroScience, Inc. offers testing that assesses both natural killer cell count (5079), NK cell activity (3014), or both (5067). Now let’s say you run one of these tests on your patient and the results indicate abnormal NK cell count or activity –  how can you use this information?

First, a few words about natural killer cells (arguably the coolest-sounding immune cells, and quite pretty as well!). NK cells basically function by distinguishing “self” (our healthy cells) from “non-self” (self-cells that are virally-infected or cancerous, or bacteria). NK cells (1) lyse (kill)  “non-self” cells, as well as (2) produce cytokines (small protein messengers) that promote helper T cell (Th1) and cytotoxic T cell mediated immunity. Bottom line, NK cells are vital players in the immune response.

Here, I’ve summarized some of the underlying reasons why your patient might have non-normal NK cell counts or function. A bit of a laundry list, but I hope that in the context of your patient’s  history and symptoms, it can help you isolate the possible root causes and design appropriate therapeutic interventions (we’ll discuss what sorts of interventions may be able to boost NK cell activity in a future post).

Low NK cell function or count – what does that tell me?

Individuals with low NK cell activity are at greater risk of severe or persistent infections and associated morbidity. Low NK cells can also result in endometriosis in women.

• Stress has been reported to lower NK cell activity, while laughter and stress reduction programs have been shown to increase NK cell activity.
• PTSD is associated with lower NK cell activity.
• Some, though not all, studies on depression suggest that it is correlated with reduced NK cell function, even as other immune parameters may be activated.
• In CFIDS (chronic fatigue immune dysfunction syndrome), NK cell activity correlates inversely with clinical severity. A number of other studies such as this one agree that NK cell activity is reduced in chronic fatigue syndrome (CFS), though NK cell count may not be different from normal controls.
• Some reports indicate that NK cell activity decreases with age, while others suggest that this is not per se the case, but that low NK activity with aging predicts impending morbidity.
• Micronutrient deficiencies in zinc or vitamins A, C, and D can negatively affect NK cell function (Wintergerst, 2006; Erickson, 2000).
• A diet rich in long-chain polyunsaturated fatty acids can reduce NK cell count.
• Exposure to toxic chemicals can harm NK cell activity.
• Stroke is followed by low NK cells.
• Pregnancy is accompanied by low NK cell activity (consider that the fetus is partially “non-self” and doesn’t need the scrutiny of ever-vigilant NK cells!)
• Exercise, particularly high-intensity and/or high-frequency resistance exercise, can depress NK cells (Kawada, 2010).
• Obesity and smoking are associated with decreased NK cell count and activity.
• Cancer is frequently associated with lowered NK cell activity, which some studies is correlated with poor prognosis.
• Short-term steroid (e.g. prednisolone) dosing; opioids and anesthetics used in surgery
• Angiotensin II (AngII) inhibitors may suppress NK cells
• Genetic immunodeficiency is perhaps the most rare cause of low NK count or activity, but is also the toughest to address since it is least likely to respond to interventions.

Elevated NK cell function or count – where does that come from?

Some of the consequences of elevated NK cell activity may include inflammation, for example in the gut, as well as exacerbated autoimmunity. Also, women with elevated NK cell activity and count are at risk of repeated miscarriages.

• Of course, your first suspect should be viral and bacterial infections that trigger normal NK cell activation, especially early in the course of the immune response.
• In certain autoimmune disorders such as Behçet’s disease and Sjögren’s syndrome, the number of activated NK cells activity is higher in active disease compared to inactive disease or healthy controls.
• In contrast to adults, stress may enhance NK cell function in children.
• Micronutrients such as vitamin A may elevate NK cells (Erickson, 2000; Ahmad, 2009).
• Certain probiotics enhance NK cell activity.
• Lithium enhances NK cell activity, as may selective serotonin reuptake inhibitors (SSRI’s).

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