Central nervous system administration of interleukin-6 produces splenic sympathoexcitation.
Interleukin-6 (IL-6) is a multifunctional cytokine that has been shown to play a pivotal role in centrally-mediated physiological responses including activation of the hypothalamic-pituitary-adrenal axis. Cerebral spinal fluid (CSF) concentrations of IL-6 are elevated in multiple pathophysiological conditions including Alzheimer's disease, autoimmune disease, and meningitis. Despite this, the effect of IL-6 on central regulation of sympathetic nerve discharge (SND) remains unknown which limits understanding of sympathetic-immune interactions in health and disease. In the present study we determined the effect of intracerebroventricular (i.c.v, lateral ventricle) administration of IL-6 on splenic SND in urethane-chloralose-anesthetized rats. A second goal was to determine if icv injected IL-6 enters the brain parenchyma and acts as a volume transmission signal to access areas of the brain involved in regulation of sympathetic nerve outflow. i.c.v administration of IL-6 (10 ng, 100 ng, and 400 ng) significantly and progressively increased splenic SND from control levels in baroreceptor-denervated Sprague-Dawley rats. Administration of 100-ng and 400-ng IL-6 resulted in significantly higher SND responses when compared to those elicited with a 10-ng dose. Sixty minutes following icv administration, fluorescently labeled IL-6 was not distributed throughout the parenchyma of the brain but was localized to the periventricular areas of the ventricular system. Brain sections counter-stained for the IL-6 receptor (IL-6R) revealed that IL-6 and the IL-6R were co-localized in periventricular areas adjoining the third ventricle. These results demonstrate that icv IL-6 administration increases splenic SND, an effect likely achieved via signaling mechanisms originating in the periventricular cells.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States.
Bryan G
BG
Helwig
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States.
Robin A
RA
Craig
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States.
Richard J
RJ
Fels
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States.
Frank
F
Blecha
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States. Electronic address: Kenny@vet.k-state.edu.
Michael J
MJ
Kenney
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011311:Pressoreceptors / Q000503:physiopathology / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D013154:Spleen / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D020542:Third Ventricle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D015850:Interleukin-6; D019947:Receptors, Interleukin-6