Vitamin A metabolites and immune responses of neonatal dairy calves

Abstract

<p>Vitamin A is a fat-soluble nutrient which is essential for optimal vision, growth and cell differentiation. Newborn animals have a less effective immune system than adults. Metabolites of vitamin A such as the retinoic acids (RA) modulate immune function. Newborn calves have negligible vitamin A (retinol) in the liver and circulation and high levels of a novel isomer of RA (9, 13-di-cis-RA). The objective of this dissertation was to evaluate the effect of the vitamin A status of newborn calves on their immune responsiveness. We show that physiologic concentrations of 9,13-di-cis-RA did not influence the ability of peripheral blood mononuclear leukocytes (PBMNL) from neonatal, precolostral calves to proliferate or produce polyclonal immunoglobulin M (IgM) or interferon-[gamma] (IFN-[gamma]) in response to pokeweed mitogen in vitro. Studies by others suggested that 9,13-di-cis-RA was a biologically inactive metabolite but it could generate biologically active 9-cis-RA. To prevent high RA levels in circulation, newborn calves were fed a diet deprived of fat-soluble vitamins or their precursors. This procedure prevented the rise of [alpha]-soluble vitamins metabolites such as RAs, retinol, [alpha]-tocopherol and their precursors ([beta]-carotene) in the serum of these calves when compared to controls. However, the phenotype and in vitro immune responses of PBMNL were not different between control and treated calves. We show that ratios of major histocompatibility complex (MHC) class II+ cells/CD3+ T lymphocytes, proliferation and IFN-[gamma] production by PBMNL from all calves were lowest at 1-4 days of age. Susceptibility to diseases may be enhanced during this period. Our third study indicated that the ability of PBMNL from newborn calves to produce nitric oxide (NO) (a mechanism of non-specific defense) was modulated by dietary vitamins A and E. The calves that were fed National Research Council-recommended levels of retinyl acetate (vitamin A) (or 20-fold higher levels) and d-[alpha]-tocopherol (vitamin E) but not those that were fed very low or high vitamin A or d-[alpha]-tocopheryl acetate, had PBMNL which produced NO at levels similar to adult animals. Optimal dietary vitamins A and E may be essential for the maturation of aspects of innate immunity in the newborn calf towards an adult phenotype.</p>