Modulation of growth performance in disease: reactive nitrogen compounds and their impact on cell proteins.
During life, all animals encounter situations that challenge their capability for optimal growth. In reacting to immune challenges in the form of disease, homeostatic mechanisms attempt to overcome disharmony of the body's internal environment, or simply put, stress. The overall impact of stress revolves around a dynamic relationship between the level of challenge imparted on physiological systems and the degree of host response that is mounted in 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 stress is often characterized by frank catabolism and tissue wasting. In some instances a level of stress (that might be termed a "stress breakpoint") is reached at which time the host response itself contributes to the cascade of negative effectors that further cause illness. These "breakpoint" responses are characterized by more intense acute responses to stress or a much more protracted duration of the response than would be expected given the nature of the stress. Key to understanding how growth in the young animal responds to infectious stresses is the recognition that (a) when immune responses that normally maintain health go awry, the reporters and effectors of the immune system (cytokines and the nitric oxide cascade) can contribute to stress disease processes and (b) reactive nitrogen compounds derived from the nitric oxide, as well as super oxide anion can modify intracellular proteins and block otherwise normal biochemical processes that regulate cell function. A key example of this is the loss of regulation of IGF-I by GH. As animals react more severely to disease stress, IGF-I concentrations in plasma decline progressively. Recent data derived from (LPS) challenges performed on young calves suggest that the prolonged decline in IGF-I is associated with the development of hepatic cytotoxicity localized to regions of protein nitration as identified by immunohistochemistry. Identifying biochemical criteria for disease processes provides needed guidance for the further development of intervention strategies to limit the impact of disease on growth.
Elsasser
T H
TH
U.S. Department of Agriculture, Agricultural Research Service. Growth Biology Laboratory, Beltsville, MD, USA. elsasser@ggpl.arsusda.gov
Kahl
S
S
Rumsey
T S
TS
Blum
J W
JW
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000503:physiopathology*; D016207:Cytokines / Q000502:physiology*; D004731:Endotoxins / Q000276:immunology / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D013312:Stress, Physiological / Q000276:immunology / Q000503:physiopathology / Q000662:veterinary*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone