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The importance of vitamin D for the immune system in swine

Vitamin D3 plays a central role in the immune response of swine . 25-OH D3 may be a more efficient source to improve vitamin D status of pigs than cholecalciferol.

Monday 12 March 2018 (2 months 14 days ago)

Although vitamin D3 (cholecalciferol) can be synthesized by ultraviolet irradiation of the provitamin D 7-dehydrocholesterol in the skin of pigs, this endogenous production usually does not meet the physiological demand, since pigs are typically confined in production units without access to direct sunlight. Therefore dietary vitamin D3 is the most reliable source to secure the vitamin D requirement for a successful production of swine.

After ingestion, cholecalciferol is absorbed from the intestinal tract with fats and the presence of bile salts is needed for absorption. Via the lymphatic system vitamin D3 is transported to the liver and is finally deposited in adipose tissues. In the liver cholecalciferol is converted to 25-hydroxy-cholecalciferol (25-OH-D3) and then further hydroxylated in the kidney to 1,25-dihydroxy-cholecalciferol (1,25-(OH)2-D3), which represents the active hormone. Vitamin D regulates the homeostasis of calcium and phosphorous, i.e. it increases the absorption of these minerals from the small intestine as well as their re-absorption in the renal tubules and it influences the calcification process by increasing the uptake of minerals by the bones. A dietary supplementation of 1,000 to 2,000 IU/kg feed is generally considered adequate for the various swine categories.

In all higher animals, the best-known and most dramatic endpoint of vitamin D3 undersupply is rickets. The epiphyses are enlarged; the bones of the extremities, of the vertebral column and the cranium are deformed and brittle. Animals move stiffly and hesitantly due to occurrence of lameness and muscular weakness. Other typical metabolic bone diseases are osteomalacia, osteochondrosis and osteoporosis, which are related to failure in bone mineralization and/or loss of bone mineral in pigs of various ages. More general clinical and subclinical deficiency signs in pigs are inhibition of growth, loss of weight, reduced or lost appetite and high mortality. In order to avoid such drastic problems, a sufficient supplementation with vitamin D3 is important.

It is known from classical studies with mice that vitamin D interacts with the immune system as well. Macrophages, responsible for the destruction of pathogens, can release 1,25-(OH)2-D3, which thereafter is able to modulate other cells within the immune system. For example, this locally produced 1,25-(OH)2-D3 impacts on activated T- and B-cells by promoting specific T-helper cell responses and down-regulating certain B-cell functions. Apart from being a source of 1,25-(OH)2-D3, macrophages are also potential targets for immuno-modulatory actions of this vitamin D-metabolite. 1,25-(OH)2-D3 helps to maintain macrophage populations by stimulating the differentiation of myeloid stem cells toward a macrophage phenotype. Furthermore macrophages exert enhanced antimicrobial action following treatment with 1,25-(OH)2-D3 via increased macrophage chemotaxis and intensified phagocytic killing of infectious bacteria.

More recently information has become available that cholecalciferol and more particularly its metabolites 25-OH-D3 and 1,25-(OH)2-D3 play also an important role for the immune system of swine. Since in the swine industry, infectious diseases are among the most common causes of mortality and accordingly of economic losses, particularly at weaning when piglets are most vulnerable to infection, this information deserves special attention.

One research group reported on the immune-modulating effects of 1,25-(OH)2-D3 as measured by the antigen-specific antibody responses after intramuscular immunization of pigs with human serum albumin (HSA). 1,25-(OH)2-D3 significantly enhanced the antigen-specific IgA and IgM serum responses. Higher HSA-specific IgA titers were also found in the mucosal secretions (saliva, feces and nasal) of the vitamin D3 treated animals. Furthermore, 1,25-(OH)2-D3 increased the number of antigen-specific IgA and IgG antibody-secreting cells in the local draining lymph nodes. In a follow-up study these authors observed that immunization of piglets with an Escherichia coli antigen during the suckling period could protect against an oral challenge with E. coli and that addition of 1,25-(OH)2-D3 improved this protection as measured by a reduced fecal excretion of E. coli. However under production conditions, the beneficial effects of 1,25-(OH)2-D3 can only occur, if a sufficient concentration of 25-OH-D3 as substrate for the second hydroxylation step is present in the blood circulation. Most reliably this can be achieved by a direct supplementation of 25-OH-D3 in the feed.

Another group investigated the immune cellular changes, occurring as a result of nutritional supplementation of weanling pigs with a commercial hydroxylated version of vitamin D3 (25-OH-D3; Hy·D). Piglets showed significant increases in leukocyte cell numbers, which represent immune biomarkers that are known to be tightly linked to antimicrobial defenses as well as a positive modulation of leukocyte survival and phagocytic capacity. These and other findings indicate that vitamin D3 plays a central role in the immune response of swine and that 25-OH D3 may be a more efficient source to improve vitamin D status of pigs than cholecalciferol.

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