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Title: Comparative aspects of the endotoxin- and cytokine-induced endocrine cascade influencing neuroendocrine control of growth and reproduction in farm mammals

Author
item WHITLOCK, B - AUBURN UNIVERSITY
item DANIEL, J - BERRY COLLEGE
item WILBORN, R - AUBURN UNIVERSITY
item Elsasser, Theodore
item Carroll, Jeffery - Jeff Carroll
item SARTIN, J - AUBURN UNIVERSITY

Submitted to: Reproduction in Domestic Animals
Publication Type: Review Article
Publication Acceptance Date: 5/1/2008
Publication Date: 7/15/2008
Citation: Whitlock, B.K., Daniel, J.A., Wilborn, R.R., Elsasser, T.H., Carroll, J.A., Sartin, J.L. 2008. Comparative aspects of the endotoxin- and cytokine-induced endocrine cascade influencing neuroendocrine control of growth and reproduction in farm mammals. Reproduction of Domestic Animals. 43(Suppl. 2):317-323.

Interpretive Summary: Many diseases common to farm and production animals are the product of infections with Gram-negative bacteria. The consequences of these infections are a result of the liberation of endotoxin/LPS from the bacteria and the reaction of the immune system/inflammatory cells. Cytokine (e.g. IL-I and TNF-alpha) production by inflammatory cells in response to LPS is a normal and necessary function of the immune system to protect animals from and alleviate infections. However, the inflammatory cytokines can also initiate a cascade of events that impair hormonal and metabolic homeostatic processes regulating growth, metabolism, and reproduction. This review article highlights these interactions and proposes that the purpose for impairing these functions is most likely a consequence of the lofty nutrient/metabolic demands for the immune system’s response to infections. In an attempt to redirect or conserve nutrients for immune functions, growth is impaired by direct or indirect actions of cytokines on the somatotropic axis. In adult animals, nutrients may be conserved by inhibiting energetically risky behavior [i.e., reproduction (estrus, pregnancy, lactation)] through manipulation of the hypothalamic-pituitary-gonadal axis at any point. More work is needed to completely understand the mechanisms behind the effects of the stress of disease on growth, metabolism, and reproduction. While previous data on severe proinflammatory mediated dysfunction was associated with stark pathology, the nitration concept follows closely with perturbations associated with low-level responses to immune challenge that don’t culminate in death. By understanding the intricacies of LPS-induced cytokine release and how cytokines affect farm animal production, we can target more precisely the strategies needed to combat infectious agents as well as stabilize host responses to infection in order to speed recovery and improve animal welfare.

Technical Abstract: Disease in animals is a well-known inhibitor of growth and reproduction. Earlier studies were initiated to determine the effects of endotoxin on pituitary hormone secretion. These studies found that in sheep, growth hormone (GH) concentration was elevated, whereas insulin-like growth factor-I (IGF-I) was inhibited, as was luteinizing hormone (LH). Examination of the site of action of endotoxin in sheep determined that somatotropes expressed the endotoxin receptor (CD14) and that both endotoxin and interleukin-I-beta activated GH secretion directly from the pituitary. In the face of elevated GH, there is a reduction of IGF-I in all species examined. Since GH cannot activate IGF-I release during disease, there appears to be a downregulation of GH signaling at the liver, perhaps related to altered nitration of janus kinase (JAK). In contrast to GH downregulation, LH release is inhibited at the level of the hypothalamus. New insights have been gained in determining the mechanisms by which disease perturbs growth and reproduction, particularly with regard to nitration of critical control pathways and perhaps serving as a new mechanism central to LPS suppression of all signaling pathways. This pathway based analysis is critical to developing novel strategies to reverse the detrimental effect of disease on animal production.