Recent evidence indicates that leukocytic-derived hormones (i.e., cytokines) provide an important signaling pathway to sympathetic neural circuits. However, the central pathways involved in mediating sympathetic nerve discharge (SND) responses to interleukin-1 beta, a proinflammatory cytokine, and the functional significance of IL-1 beta-mediated SND responses remain poorly defined. These are significant omissions because the elaboration of mechanisms by which the immune system alters SND is critical for understanding the role of autonomic-immune interactions in physiological regulation and disease processes.
Specific Aim 1 : To identify central neural sites involved in mediating SND responses to IL-1 beta. We will test the hypotheses that a) different levels of the supraspinal neuraxis mediate regionally-selective SND responses to IL-1 beta, b) paraventricular nucleus neurons are critically involved in mediating forebrain-dependent SND responses to IL-1 beta, c) the ventral lateral medulla is a key brainstem site mediating SND responses to IL-1 beta, and d) circum-ventricular organs are part of the central circuitry involved in mediating SND responses to peripheral IL-1 beta.
Specific Aim 2 : To determine target organ effects of IL-1 beta. We hypothesize that IL-1 beta administration produces no uniform changes in arterial blood flow to regionally-selective circulations and that activation of splenic nerve efferents induces cytokine gene expression which enhances the immune capability of the organism. Electrophysiological, central nervous system microinjection, frequency-domain analytical and molecular biological techniques will be used to complete these studies. The experimental approach described in this proposal will help unravel the regulatory controls of the immune and sympathetic nervous systems. Ultimately, these findings may allow for the design of intervention strategies in immune regulation fostering robust and appropriate communication between the immune and nervous systems.
| Helwig, Bryan G; Craig, Robin A; Fels, Richard J et al. (2008) Central nervous system administration of interleukin-6 produces splenic sympathoexcitation. Auton Neurosci 141:104-11 |
| Barman, Susan M; Kenney, Michael J (2007) Methods of analysis and physiological relevance of rhythms in sympathetic nerve discharge. Clin Exp Pharmacol Physiol 34:350-5 |
| Helwig, Bryan G; Musch, Timothy I; Craig, Robin A et al. (2007) Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 292:R1165-73 |
| Ganta, Chanran K; Helwig, Bryan G; Blecha, Frank et al. (2006) Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system. Am J Physiol Regul Integr Comp Physiol 291:R558-65 |
| Helwig, Bryan G; Parimi, Sujatha; Ganta, Chanran K et al. (2006) Aging alters regulation of visceral sympathetic nerve responses to acute hypothermia. Am J Physiol Regul Integr Comp Physiol 291:R573-9 |
| Ganta, Chanran K; Lu, Ning; Helwig, Bryan G et al. (2005) Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Am J Physiol Heart Circ Physiol 289:H1683-91 |
| Lu, Ning; Helwig, Bryan G; Fels, Richard J et al. (2004) Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II. Am J Physiol Heart Circ Physiol 287:H2626-33 |
| Ganta, Chanran K; Blecha, Frank; Ganta, Roman R et al. (2004) Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Physiol Genomics 19:175-83 |
| Lu, Ning; Wang, Yan; Blecha, Frank et al. (2003) Central interleukin-1beta antibody increases renal and splenic sympathetic nerve discharge. Am J Physiol Heart Circ Physiol 284:H1536-41 |
| Kenney, Michael J; Weiss, Mark L; Mendes, Tammy et al. (2003) Role of paraventricular nucleus in regulation of sympathetic nerve frequency components. Am J Physiol Heart Circ Physiol 284:H1710-20 |
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