Information emerging from basic and clinical studies demonstrates that the nervous system superimposes the same type of control on the immune system as it does on the endocrine system, and it seems likely that some type of feedback mechanisms are present. To prove the hypothesis that the immune system is under regulatory control of the nervous system, specific pathways and control mechanisms must be demonstrated. The proposed studies will examine the chronology of neuroendocrine-immune connections that already exist or may emerge in young adult rats after several different experimental manipulations of the Anterior Hypothalamic Area (AHA). The manipulations will include: stimulation, electrolytic lesions or deafferentation of the AHA. The observations will be planned to establish whether AHA manipulations produce changes in neuroendocrine axes regulating prolactin (Prl), adrenocortical trophic hormone (ACTH) and opioid beta- endorphin (betaEnd) hormone release into the peripheral blood, and to relate these changes to those of the thymus gland function in vivo. In addition, in vitro studies involving perfusion of either 1) the preoptic area-mediobasal hypothalamus and thymus after brain stimulation or lesion. Specific experiments include: 1) repeated measures over 30d of plasma Prl, ACTH corticosterone and beta-End in the blood of rats that have received one of the following AHA manipulations: a) chronic electrical stimulation; b) electrolytic lesions; c) chemical lesions produced by N-methyl-DL- asparate; or d) anterolateral deafferentation. A study of thymus size and lymphocyte sub-population will be included; 2) Acute (1-4hr) and longer term (48-72hrs) neuroendocrine and thymus responses to intravenous endotoxin challenge after a-d AHA manipulations; 3) in vitro perfusion of POA-MBH fragments at selected intervals after a-d AHA manipulations and measurement of corticotropin releasing hormone (CRH), vasoactive intestinal peptide (VIP), dopamine and interleukin-1 release; 4) in vitro perfusion of thymus gland removed from rats after AHA manipulations to study release of VIP, norepinephrine and thymosin alpha1.
| Phelps, C P; Dong, J M; Chen, L T et al. (2001) Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to endotoxin after damage of the anterior hypothalamic area. Neuroimmunomodulation 9:340-51 |
| Ma, X C; Chen, L T; Oliver, J et al. (2000) Cytokine and adrenal axis responses to endotoxin. Brain Res 861:135-42 |
| Menzies, R; Phelps, C; Wiranowska, M et al. (1996) The effect of interferon-alpha on the pituitary-adrenal axis. J Interferon Cytokine Res 16:619-29 |
| Phelps, C P; Chen, L T; Oliver, J et al. (1995) Variable tissue reactions and endocrine responses to a jugular catheter. J Submicrosc Cytol Pathol 27:83-9 |
| Phelps, C P; Sahu, A; Oliver, J et al. (1995) In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling. Brain Res 688:193-7 |
| Sahu, A; Phelps, C P; White, J D et al. (1992) Steroidal regulation of hypothalamic neuropeptide Y release and gene expression. Endocrinology 130:3331-6 |
