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

¹ United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705
² Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849

^* To whom correspondence should be addressed. E-mail: elsasser{at}anri.barc.usda.gov.

	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 the proinflammatory response (PR), the biochemical effects of the resulting cascade of PR mediators [cytokines, prostaglandin and prostacyclin derivitives, nitric oxide (NO), superoxide anion (O₂·), etc.] override the regulatory signals normally ascribed to anabolic tissue accretion and growth. The efficiency of energy and nutrient use will proportionally decrease for growth rate due to the redirection of nutrient use to support immune defense processes. These proinflammatory events can develop in association with infectious disease but also are apparent in and a part of the natural response to 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 although traditional clinical markers of PR are no longer evident. Recent evidence indicates that the PR cascades initiated by cytokines like tumor necrosis factor- play a major role in these growth deficits. Perturbations in mitochondrial energetics and NO and O₂· generation and interaction further affect metabolic balance. Free radicals and reactive nitrogen intermediates interact with select molecular targets in proteins (i.e., enzymes, histone proteins, and signal transduction proteins), causing the nitration and nitrosylation of select amino acids. If these posttranslational modifications occur in proteins associated with control points critical in metabolic stability, the resulting altered protein structure blocks it's functionality. Attenuation of these overt post-translational protein modification at their site of production offers a strategy to minimize their detrimental impact while preserving needed cytokine, NO, and O₂· functions.

Key Words: Cytokine, metabolism, nitric oxide, peroxynitrite, proinflammatory response, tyrosine nitration