Critical control points in the impact of proinflammatory immune response on growth and metabolism

Authors: Elsasser, Theodore; Caperna, Thomas; Li, Congjun - Cj; Kahl, Stanislaw; SARTIN, J - AUBURN UNIVERSITY

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2008
Publication Date: 4/1/2008
Citation: Elsasser, T.H., Caperna, T.J., Li, C.J., Kahl, S., Sartin, J.L. 2008. Critical control points in the impact of the proinflammatory immune response on growth and metabolism. Journal of Animal Science. 86(E. Suppl):E105-E 125.

Interpretive Summary: Good animal management entails limiting the impact of natural and production stress on animals in order to ensure that growth of young animals is efficient. If scientists can determine what biochemical and metabolic pathways are affected by the stress, fact-driven strategies can be developed to intervene in stress reactions and reinforce good economic return. A series of experiments were conducted on cattle to assess how different physiological states affect the function and expression of several genes and proteins that generate the free radicals that harm cells during the stress response to infectious agents or the toxins that some of these microbes release when they invade. We learned that a major source of poor metabolism that develops during the stress response is associated with the generation of what are called “nitrated proteins” – proteins to which nitrate groups are attached as a result of the over production of very reactive nitrogen and oxygen compounds produced in an affected animal’s cells. These nitrations alter, and in some cases completely block, gene expression and protein function causing what we define as disease. We determined that dietary components modulate the generation of nitrated proteins by providing more or less of an amino acid called arginine (a nutrient from which reactive nitrogen compounds are generated) as well as changing the levels of activity of enzyme pathways that also use the arginine. Data suggest that a sound recommendation can be made to use natural vitamin E to eliminate some of the bad effects of the reactive nitrogen and oxygen compounds based on the ability of vitamin E to adsorb free radicals. It appears that the administration of vitamin E in anticipation of an animal’s exposure to either natural or management-associated sources of stress is most beneficial. When this is done, the levels of nitrated proteins decrease significantly; the duration and magnitude of impact of the stress response on growth metabolism is shortened.

Technical Abstract: Intrinsic in the equation for successful animal production is the efficiency of nutrient use for assimilation into useful animal-derived product. However, when young, growing animals encounter various stressors that activate components of the innate immune system, the resulting cytokine milieu needed to initiate and coordinate the proinflammatory response (PR) against the threat overrides the regulatory signals normally ascribed to anabolic tissue accretion and growth. The efficiency of nutrient use will proportionally decrease for growth rate at the expense of the redirection of nutrient use to support immune response tissues and processes. These proinflammatory events can develop in association with infectious disease and infestation but also are apparent in and a part of the response to vaccination and the natural and management processes of birth, parturition, and weaning. If growth patterns are tracked during the PR, growth deficits are often apparent. Some growth deficits are relatively transient in duration while others are quite long lasting, persisting though traditional clinical markers of PR are no longer evident. Recent evidence suggests that the PR cascades initiated by cytokines like tumor necrosis factor-a play a major role in these growth deficits in concert with nitric oxide synthase (NOS) isoforms and superoxide anion generation; where the cascade tends to respond outside of the spatial and temporal constraints normally ascribed to nitric oxide (NO) and its metabolites, the interaction of free radicals and reactive nitrogen intermediates with select molecular targets in proteins (i.e., enzymes and signal transduction proteins) associated with control points critical to metabolic stability causes the nitration and nitrosylation of select amino acids altering their functionality.