Modulation of growth performance in disease: reactive nitrogen compounds and their impact on cell proteins

During life, all animals encounter situations that challenge their capabili ty for optimal growth. In reacting to immune challenges in the form of dise ase, homeostatic mechanisms attempt to overcome disharmony of the body's in ternal environment, or simply put, stress. The overall impact of stress rev olves around a dynamic relationship between the level of challenge imparted on physiological systems and the degree of host response that is mounted i n the process of detecting and reacting to the stress. In growing animals, the majority of milder stress encounters are manifest in terms of energetic inefficiencies and periods of reduced anabolism. In contrast, severe stres s is often characterized by frank catabolism and tissue wasting. In some in stances a level of stress (that might be termed a "stress breakpoint") is r eached at which time the host response itself contributes to the cascade of negative effecters that further cause illness. These "breakpoint" response s are characterized by more intense acute responses to stress or a much mor e protracted duration of the response than would be expected given the natu re of the stress. Key to understanding how growth in the young animal respo nds to infectious stresses is the recognition that (a) when immune response s that normally maintain health go awry, the reporters and effecters of the immune system (cytokines and the nitric oxide cascade) can contribute to s tress disease processes and (b) reactive nitrogen compounds derived from th e nitric oxide, as well as super oxide anion can modify intracellular prote ins and block otherwise normal biochemical processes that regulate cell fun ction. A key example of this is the loss of regulation of IGF-I by GH. As a nimals react more severely to disease stress, IGF-I concentrations in plasm a decline progressively. Recent data derived from (LPS) challenges performe d on young calves suggest that the prolonged decline in IGF-I is associated with the development of hepatic cytotoxicity localized to regions of prote in nitration as identified by immunohistochemistry. Identifying biochemical criteria for disease processes provides needed guidance for the further de velopment of intervention strategies to limit the impact of disease on grow th. (C) 2000 Elsevier Science inc. All rights reserved.