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SELENIUM & IMMUNITY

Immunity and the immune system comprise a complex web of interactive processes that act together to protect us from invading pathogens and malignancy. It is well established that dietary Selenium (Se) is important for a healthy immune response to infections, and its contribution to the integrity of the immune system is a major feature of its nutritional role. It is apparent that cells of the immune system have a functional requirement for Se. Furthermore, the mRNAs of several T-cell-associated genes have the ability to encode selenoproteins, which indicates that Se may have more roles in the immune system than previously thought (Taylor & Nadimpalli, 1999).

Se deficiency reduces immunocompetence, involving impairment of neutrophil, macrophage and polymorphonuclear leukocyte activity (Boyne & Arthur, 1986; Dimitrov et al. 1984; Spallholz et al. 1990).  Se supplementation of even supposedly Se-replete individuals is immunostimulatory, and involves enhancement of natural-killer-cell and lymphocyte activity as well as enhancement of proliferation of activated T-cells.  Lymphocytes from people supplemented with Se at 200 micrograms/day showed an increased response to antigens and more than doubled the ability to destroy tumour cells.  In addition, natural killer cell activity was nearly doubled (Kiremidjian-Schumacher et al, 1994).

The effect of Se on neutrophil function has been thoroughly investigated.  Neutrophils must achieve a balance between producing enough free radicals to kill invading microorganisms while avoiding damage to themselves.  Neutrophils from Se-deficient animals are less able to destroy pathogens than are neutrophils from Se-sufficient animals (Boyne & Arthur, 1986).  The ability of the neutrophils to continue to produce radicals depends on increased Se status and glutathione peroxidase activity.  It is apparent that there are multiple Se-dependent functions that regulate the ability of immune cells to kill ingested microbes (Arthur et al, 2003).

Neutrophil function in the body is also likely to be influenced by endocrine factors.  Thyroid hormone metabolism is impaired by Se deficiency  Hypothyroidism inhibits immune function, in part by reducing the ability of neutrophils to respond to challenges (as seen in the case of Se deficiency, above).  Moreover, inhibition of deiodinase activity, as can occur under Se deficiency, could impact on the immune system by inhibiting development and function of thymus cells (Arthur et al, 2003).  Finally, Se has both direct anti-viral effects, particularly against RNA viruses (which include the HIV retrovirus) [link to Anti-viral page], and various direct anti-cancer effects [link to Anti-cancer page].  These effects will obviously be of assistance to the immune response to pathogens and to cells that are likely to develop into tumours.

The strongest evidence for Se’s importance to the human immune system comes from a recent study in the United Kingdom, where adults with marginal Se status were supplemented with either 50 or 100 micrograms/day Se, compared to a placebo group.  All individuals received a live attenuated poliomyelitis vaccine after six weeks.  The trial found that Se supplementation enhanced the cellular immune response through increased production of gamma-interferon and other cytokines, an earlier peak T-cell proliferation, and an increase in T helper cells.  Furthermore, the Se-supplemented individuals cleared the virus faster, and the virus showed a lower mutation rate (and thus was less likely to become more virulent) in these people.  There was a dose-response: the higher Se dose worked better than the lower dose, and it appeared that even more Se would have been beneficial.  Indeed, the authors concluded that even “the additional 100 micrograms Se/day may be insufficient to support optimal function (Broome et al, 2004). [link to How Much Selenium page].

Importantly, Se is able to reverse the age-related decline in immune response in the elderly.  In a group of institutionalised elderly people supplemented with 100 micrograms Se (in the form of Se-enriched yeast, where most Se is in the selenomethionine form) per day for six months, immune response to mitagen challenge was restored to the level of that in healthy young individuals (Peretz et al, 1991).  In another study involving elderly people, a nutritional supplement that included Se reduced symptoms of upper respiratory tract infection and increased immune response (Langkamp-Henken et al, 2004).

In conclusion, it is clear that adequate dietary Se is essential for the activity of virtually all aspects of the immune system.

Definitions

Leukocyte: white blood cell, most of which are involved in immunity

Lymphocyte: a type of white blood cell formed in lymph tissue.

Phagocyte: a leukocyte cell that engulfs and destroys invading microorganisms

Macrophage: a large phagocytic cell occurring in the blood, lymph and connective tissue

Polymorphonuclear leukocyte: blood phagocyte that can leave the blood and migrate to extravascular sites of infection and inflammation.

Neutrophil: a leukocyte with a lobed nucleus that stains with neutral dyes.

Natural killer cell: a leukocyte that is activated by double-stranded RNA and fights viral infections and tumours.

T-cell: a lymphocyte that matures in the thymus and is responsible for cell-mediated immunity.

B-cell: a lymphocyte that matures in bone marrow.  In the presence of an antigen it becomes more active, transforms into a plasma cell and produces antibodies.

Cytokines: regulatory proteins released by cells of the immune system that serve to generate an immune response.

References

Arthur JR, McKenzie RC, Beckett GJ 2003. Selenium in the immune system. J Nutr 133: 1457S-1459S.

Boyne R, Arthur J 1986. The response of selenium-deficient mice to Candida albicans infection. J Nutr 116: 816-822.

Broome CS, McArdle F, Kyle JAM, Andrews F, Lowe NM, Hart CA, Arthur JA, Jackson MJ 2004. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 80: 154-162.

Dimitrov N, Meyer C, Ullrey D 1984. Selenium is a metabolic modulator of phagocytosis. In Combs G, Levander O, Spallholz J, Oldfield J (eds) Selenium in biology and medicine, 254-262. New York: AVI Publishing Co.

Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G 1994. Supplementation with selenium and human immune cell functions. Biol Trace Elem Res 41: 115-127.

Langkamp-Henken B, Bender BS, Gardner EM, Herrlinger-Garcia KA, Kelley MJ, Murasko DM, Schaller JP, Stechmiller JK, Thomas DJ, Wood SM 2004. Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors. J Am Geriatr Soc 52(1): 3-12.

Peretz A, Neve J, Desmedt J, Duchateau J, Dramaix M, Famaey JP 1991. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am J Clin Nutr 53: 1323-1328.

Spallholz JE, Boylan LM, Larsen HS 1990. Advances in understanding selenium’s role in the immune system. Ann N Y Acad Sci 587: 123-139.

Taylor EW, Nadimpalli RG 1999. Chemoprotective mechanisms of selenium in cancer and AIDS: evidence for the involvement of novel selenoprotein genes. Info Onkologi 2: 7-11.

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Laucke Flour Mills Pty Ltd
Strathalbyn, South Australia
Bridgewater on Loddon, Victoria
2 Callington Rd Strathalbyn SA 5255
PO Box 200 Strathalbyn SA 5255
E-mail: bread@laucke.com.au
Phone: (08) 8536 5555
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