This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Turnbull, A. V. Articles by Rivier, C. L. Search for Related Content PubMed PubMed Citation Articles by Turnbull, A. V. Articles by Rivier, C. L.

Intracerebroventricular Passive Immunization. I. The Effect of Intracerebroventricular Administration of an Antiserum to Tumor Necrosis Factor- on the Plasma Adrenocorticotropin Response to Lipopolysaccharide in Rats¹

The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Catherine L. Rivier, The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu

The present study tested the hypothesis that the cytokine tumor necrosis factor- (TNF-) is an important central nervous system mediator of the rat hypothalamo-pituitary-adrenal (HPA) axis response to the iv administration of lipopolysaccharide (LPS; 5 µg/kg). LPS produced a rapid (within 30 min) rise in plasma TNF- levels, which preceded elevations in plasma ACTH (commencing at 45 min). Despite a lack of detectable TNF- biological activity in the brain 30 min to 2 h after LPS administration, intracerebroventricular (icv) pretreatment (-20 h) with 5 µl anti-TNF- antiserum significantly delayed the onset of the plasma ACTH response to LPS, suggesting that TNF- acts within the brain. However, we also noted that the icv infusion of anti-TNF- 20 h earlier produced experimentally significant concentrations of the same anti-TNF- antibodies in systemic blood. This suggested the possibility that the effect of this antiserum was due to its leakage to the periphery. Indeed, 5 µl anti-TNF- administered iv at -20 h produced an inhibition of the ACTH response to LPS that was temporally and quantitatively similar to that produced by icv anti-TNF-. Intracerebroventricular administration of anti-TNF- immediately before LPS produced only low systemic blood levels of corresponding anti-TNF- antibodies and did not significantly alter the plasma ACTH response, whereas iv administration of anti-TNF- immediately before LPS was clearly effective. Collectively, these results show that 1) biologically active levels of TNF- in systemic plasma and the ensuing ACTH responses to LPS were always temporally and qualitatively related; and 2) even though icv administration of anti-TNF- could inhibit the HPA axis response to LPS, this was apparent only when substantial amounts of anti-TNF- antibodies had reached systemic blood. We, therefore, conclude that at the dose of LPS used in this study (5 µg/kg), TNF- is an important mediator of the HPA axis response to LPS by an action within the periphery, but probably not within the brain.

This article has been cited by other articles:

				M. Herman and C. Rivier Activation of a Neural Brain-Testicular Pathway Rapidly Lowers Leydig Cell Levels of the Steroidogenic Acute Regulatory Protein and the Peripheral-Type Benzodiazepine Receptor while Increasing Levels of Neuronal Nitric Oxide Synthase Endocrinology, January 1, 2006; 147(1): 624 - 633. [Abstract] [Full Text] [PDF]

				A. Rossi-George, D. Urbach, D. Colas, Y. Goldfarb, and A. W. Kusnecov Neuronal, Endocrine, and Anorexic Responses to the T-Cell Superantigen Staphylococcal Enterotoxin A: Dependence on Tumor Necrosis Factor-{alpha} J. Neurosci., June 1, 2005; 25(22): 5314 - 5322. [Abstract] [Full Text] [PDF]

				S. Lee, D. Selvage, K. Hansen, and C. Rivier Site of Action of Acute Alcohol Administration in Stimulating the Rat Hypothalamic-Pituitary-Adrenal Axis: Comparison between the Effect of Systemic and Intracerebroventricular Injection of this Drug on Pituitary and Hypothalamic Responses Endocrinology, October 1, 2004; 145(10): 4470 - 4479. [Abstract] [Full Text] [PDF]

				D. J. Selvage, S. Y. Lee, L. H. Parsons, D. O. Seo, and C. L. Rivier A Hypothalamic-Testicular Neural Pathway Is Influenced by Brain Catecholamines, But Not Testicular Blood Flow Endocrinology, April 1, 2004; 145(4): 1750 - 1759. [Abstract] [Full Text] [PDF]

				K. M. Ogilvie, R. Saladin, T. R. Nagy, M. S. Urcan, R. A. Heyman, and M. D. Leibowitz Activation of the Retinoid X Receptor Suppresses Appetite in the Rat Endocrinology, February 1, 2004; 145(2): 565 - 573. [Abstract] [Full Text] [PDF]

				H. Yang, K. Kawakubo, H. Wong, G. Ohning, J. Walsh, and Y. Tache Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G575 - G581. [Abstract] [Full Text] [PDF]

				S. Rivest, S. Lacroix, L. Vallières, S. Nadeau, J. Zhang, and N. Laflamme How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli Experimental Biology and Medicine, January 1, 2000; 223(1): 22 - 38. [Abstract] [Full Text]

				S. Hayley, K. Brebner, S. Lacosta, Z. Merali, and H. Anisman Sensitization to the Effects of Tumor Necrosis Factor-alpha : Neuroendocrine, Central Monoamine, and Behavioral Variations J. Neurosci., July 1, 1999; 19(13): 5654 - 5665. [Abstract] [Full Text] [PDF]

				K. Ogilvie and C. Rivier The Intracerebroventricular Injection of Interleukin-1{beta} Blunts the Testosterone Response to Human Chorionic Gonadotropin: Role of Prostaglandin- and Adrenergic-Dependent Pathways Endocrinology, July 1, 1998; 139(7): 3088 - 3095. [Abstract] [Full Text] [PDF]