Splenic Denervation Blocks Leptin-Induced Enhancement of Humoral Immunity in Siberian Hamsters (Phodopus sungorus)Demas G.E.
Department of Biology, Program in Neural Science, and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, Ind., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Nontropical rodents have evolved adaptations to maximize winter survival, including alterations in reproduction, energy balance and immunity. Short-day-housed Siberian hamsters display reductions in body fat and decreases in humoral immunity compared with long-day hamsters. The hormone leptin, secreted by adipose tissue, varies in response to changes in body fat and has been implicated in photoperiodic changes in immunity. In addition, the metabolic effects of this hormone appear to be mediated by the sympathetic nervous system (SNS). Very little is known, however, regarding the role of the SNS in regulating the effects of leptin on immunity. The goal of the present study was to examine the effects of splenic denervation on leptin-induced immune enhancement of short-day Siberian hamsters. Male hamsters were housed in long (LD 16:8) or short days (LD 8:16) for 10 weeks. Half of the animals in each photoperiod received surgical denervations of the spleen; the remaining animals received sham operations. In addition, animals in each group were implanted with osmotic minipumps containing either leptin or vehicle. Hamsters were then injected with keyhole limpet hemocyanin (KLH) and serum anti-KLH antibody production was assessed. Short-day hamsters displayed decreased humoral immunity in short versus long days; leptin attenuated the short-day decrease but did not enhance immunity of long-day hamsters. Furthermore, splenic denervation blocked the leptin-induced increase in immunity in short-day hamsters. Collectively, these data suggest that leptin plays an important role in regulating seasonal changes in humoral immunity of Siberian hamsters and the effects of leptin occur, at least in part, via changes in the SNS innervation of lymphoid tissue.
© 2002 S. Karger AG, Basel
Bronson F, Heideman PD: Seasonal regulation of reproduction in mammals; in Knobil E, Neill JD (eds): The Physiology of Reproduction, ed 2. New York, Raven Press, 1994, vol 2, pp 541–584.
- Maier SF, Watkins LR, Fleshner M: Psychoneuroimmunolgy: The interface between behavior, brain, and immunity. Am Psychol 1994;49:1004–1017.
- Demas GE, Chefer VC, Talan MI, Nelson RJ: Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. Am J Physiol 1997;273:R1631–R1637.
Lochmiller RL, Deerenberg C: Trade-offs in evolutionary immunology: Just what is the cost of immunity? Oikos 2000;88:87–98.
- Nelson RJ, Demas GE: Seasonal changes in immune function. Q Rev Biol 1996;71:511–548.
- Sheldon BC, Verhulst S: Ecological immunology: Costly parasite defenses and trade-offs in evolutionary ecology. TREE 1996;11:317–321.
- Woods SC, Seeley RJ: Adiposity signals and the control of energy homeostasis. Nutrition 2000;16:894–902.
- Van Dijk G: The role of leptin in the regulation of energy balance and adiposity. J Neuroendocrinol 2001;13:913–921.
- Drazen DL, Demas GE, Nelson RJ: Leptin effects on immune function and energy balance are photoperiod dependent in Siberian hamsters (Phodopus sungorus). Endocrinology 2001;142:2768–2775.
Havel PJ: Peripheral signals conveying metabolic information to the brain: Short-term and long-term regulation of food intake and energy homeostasis. Exp Biol Med 2001;226:963–977.
- Elmquist JK: Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav 2001;74:703–708.
- Mizuno A, Murakami T, Otani S, Kuwajima M, Shima K: Leptin affects pancreatic endocrine functions through the sympathetic nervous system. Endocrinology 1998;139:3863–3870.
- Rayner DV: The sympathetic nervous system in white adipose tissue regulation. Proc Nutr Soc 2001;60:357–364.
- Scarpace PJ, Matheny M, Moore RL, Kumar MV: Modulation of uncoupling protein 2 and uncouplin protein 3: Regulation by denervation, leptin and retinoic acid treatment. J Endocrinol 2000;164:331–337.
- Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI: Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998;394:897–901.
- Faggioni R, Fantuzzi G, Gabay C, Moser A, Dinarello CA, Feingold KR, Grunfeld C: Leptin deficiency enhances sensitivity to endotoxin-induced lethality. Am J Physiol 1999;276:R136–R142.
- Finck BN, Kelley KW, Dantzer R, Johnson RW: In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha in the induction of leptin by lipopolysaccharide. Endocrinology 1998;139:2278–2283.
Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM: Leptin regulates proinflammatory immune responses FASEB J 1998;12:57–65.
- Takahashi N, Waelput W, Guisez Y: Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor. J Exp Med 1999;189:207–212.
- Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD: The timed infusion paradigm for melatonin delivery: What has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? J Pineal Res 1993;15:161–190.
- Goldman BD: The Siberian hamster as a model for study of the mammalian photoperiodic mechanism. Adv Exp Med Biol 1999;460:155–164.
- Demas GE, Drazen DL, Jasnow AM, Bartness TJ, Nelson RJ: Sympathoadrenal system differentially affects photoperiodic changes in immune function in Siberian hamsters (Phodopus sungorus). J Neuroendocrinol 2002;14:29–35.
Drazen DL, Kriegsfeld LJ, Schneider JE, Nelson RJ: Leptin, but not immune function, is linked to reproductive responsiveness to photoperiod. Am J Physiol 2000;278:R1401–R1407.
- Yellon SM, Fagoaga OR, Nehlsen-Cannarella SL: Influence of photoperiod on immune cell functions in the male Siberian hamster. Am J Physiol 1999;276:R97–R102.
- Okamoto S, Irie Y, Ishikawa I, Kimura K, Saito M: Central leptin suppresses lymphocyte functions through activation of the corticotrophin-releasing hormone-sympathetic nervous system. Brain Res 2000;855:192–197.
- Williams JM, Peterson RG, Shea PA, Schmedtje JF, Bauer DC, Felten DL: Sympathetic innervation of murine thymus and spleen: Evidence for a functional link between the nervous and immune systems. Brain Res Bull 1981;6:83–94.
- Dixon FJ, Jacot-Guillarmod H, McConahey PJ: The antibody responses of rabbits and rats to hemacyanin. J Immunol 1966;97:350–355.
- Bilbo SD, Drazen DL, Quan N, He L, Nelson RJ: Short day lengths attenuate the symptoms of infection in Siberian hamsters. Proc Roy Soc Lond [B] 2001;269:447–454.
Bellinger DL, Lorton D, Luhahn C, Felten DL: Innervation of lymphoid organs: Association of nerves with cells of the immune system and their implications in disease; in Ader R, Felten DL, Cohen N (eds): Psychoneuroimmunology, ed 3. New York, Academic Press, 2001, pp 55–111.
Sanders VM, Kasprowicz DH, Kohm AP, Swanson MA: Neurotransmitter receptors on lymphocytes and other lymphoid tissues; in Ader R, Felten DL, Cohen N (eds): Psychoneuroimmunology, ed 3. New York, Academic Press, 2001, pp 161–196.
- Miles K, Quintans, J Chelmicka-Schorr E, Arnason BG: The sympathetic nervous system modulates antibody response to thymus-independent antigens. J Neuroimmunol 1981;1:101–105.
- Depelchin A, Letesson JJ: Adrenaline influence on the immune response. I. Accelerating or suppressor effects according to the time of applications. Immunol Lett 1981;3:199–205.
Kruszewska B, Felten DL, Stevens SY, Moynihan JA: Sympathectomy-induced immune changes are not abrogated by the glucocorticoid receptor blocker RU-486. Brain Behav Immunol 1998;12:181–200.
- Kohm AP, Sanders VM: Norepinephrine: A messenger from the brain to the immune system. Immunol Today 2000;21:539–542.
- Livnat S, Felten SY, Carlson SL, Bellinger DL, Felten DL: Involvement of peripheral and central catecholamine systems in neural-immune interactions. J Neuroimmunol 1985;10:5–30.
- Fuchs BA, Albright JW, Albright JF: β-Adrenergic receptors on murine lymphocytes: Density varies with cell maturity and lymphocyte subtype and is decreased after antigen administration. Cell Immunol 1988;114:231–245.
- Elenkov IJ, Wilder RJ, Chrousos GP, Vizi ES: The sympathetic nerve: An integrative interface between two supersystems: The brain and the immune system. Pharmacol Rev 2000;52:595–638.
- Blalock JE: The immune system as a sensory organ. J Immunol 1984;132:1067–1070.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.