Background: Although bronchial asthma is well known as an inflammatory disease that shows obvious circadian rhythms of airway narrowing, it remains to be elucidated whether the suprachiasmatic nucleus (SCN), a major circadian pacemaker, regulates inflammatory mediators relevant to asthma. Thus, we investigated the effects of electrolytic lesioning of the SCN on the antigen-induced immediate allergic response and the late allergic response (LAR) in male Brown Norway rats, i.e. in a model of allergic inflammation. Methods: The immediate allergic response, assessed by the histamine levels in plasma and bronchoalveolar lavage fluid (BALF), and the LAR, assessed by the eosinophilic infiltration into BALF and the lamina propria mucosae of the left main bronchus, were examined in three groups of 18 rats each, including (1) an unoperated control group, (2) a sham SCN-lesioned group, and (3) an SCN-lesioned group. Results: Both the plasma histamine levels and the number of eosinophils in bronchial tissues in the SCN-lesioned group were significantly lower than those in the other groups. The concentration of histamine and the number of eosinophils in the right BALF showed a similar pattern; however, no significant differences were found. Both plasma adrenaline and noradrenaline levels were highest during the LAR, whereas the corticosterone level was lowest in the SCN-lesioned group; again, no significant differences were obtained. Conclusions: These findings indicate that the SCN has a significant effect on the inflammatory mediators relevant to bronchial asthma.

Keywords:
Bronchial asthma, Circadian rhythm, Corticosterone, Eosinophil, Histamine
1.
Skloot GS: Nocturnal asthma: mechanisms and management. Mt Sinai J Med 2002;69:140–147.
2.
Clark TJH, Hetzel MR: Diurnal variation of asthma. Br J Dis Chest 1977;71:87–92.
3.
Martin RJ: Nocturnal asthma: circadian rhythms and therapeutic interventions. Am Rev Respir Dis 1993;147:S25–S28.
4.
Barnes P, Fitzgerald G, Brown M, Dollery C: Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N Engl J Med 1980;303:263–267.
5.
Turner-Warwick M: Epidemiology of nocturnal asthma. Am J Med 1988;85(suppl 1B):6–8.
6.
Cochrane GM, Clark TJH: A survey of asthma mortality in patients between ages 35 and 64 in the Greater London Hospitals. Thorax 1975;30:300–305.
7.
Guberan E, Williams MK, Walford J, Smith MM: Circadian variation of FEV in shift workers. Brit J Ind Med 1969;26:121–125.
8.
Rusak B, Zucker I: Neural regulation of circadian rhythms. Physiol Rev 1979;59:449–526.
9.
Meijer JH, Rietveld WJ: Neurophysiology of the suprachiasmatic circadian pacemaker in rodents. Physiol Rev 1989;69:671–707.
10.
Weaver DR: The search for circadian rhythm pacemakers in the light of lesion experiments. Chronobiologia 1978;5:69–88.
11.
Stephan FK, Zucker I: Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci USA 1972;69:1583–1586.
12.
Skoner DP, Page R, Asman B, Gillen L, Fireman P: Plasma elevations of histamine and a prostaglandin metabolite in acute asthma. Am Rev Respir Dis 1988;137:1009–1014.
13.
Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, Michel F: Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033–1039.
14.
Wardlaw AJ, Brightling CE, Green R, Woltmann G, Bradding P, Pavord ID: New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond) 2002;103:201–211.
15.
Eidelman DH, Bellofiore S, Martin JG: Late airway responses to antigen challenge in sensitized inbred rats. Am Rev Respir Dis 1988;137:1033–1037.
16.
König JFR, Klippel RA: The Rat Brain; A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Baltimore, Williams & Wilkins, 1963.
17.
Szafarczyk A, Ixart G, Malaval F, Nouguier-Soule J, Assenmacher I: Effects of lesions of the suprachiasmatic nuclei and p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma, and on locomotor activity of rats. J Endocrinol 1979;83:1–16.
18.
Irie M, Nagata S, Endo Y, Kobayashi F: Effect of rapid eye movement sleep deprivation on allergen-induced airway responses in a rat model of asthma. Int Arch Allergy Immunol 2003;130:300–306.
19.
McBride P, Bradley D, Kaliner M: Evaluation of a radioimmunoassay for histamine measurement in biologic fluids. J Allergy Clin Immunol 1988;82:638–646.
20.
Daeron M, Sterk AR, Hirata F, Ishizaka T: Biochemical analysis of glucocorticoid-induced inhibition of IgE-mediated histamine release from mouse mast cells. J Immunol 1982;129:1212–1218.
21.
Sabag N, Castrillon MA, Tchernitchin A: Cortisol-induced migration of eosinophil leukocytes to lymphoid organs. Experientia 1978;34:666–667.
22.
Alm PE, Bloom GD: Catecholamine inhibition of rat mast cell histamine secretion – a process independent of cyclic AMP levels and counteracted by glucose. Life Sci 1983;32:307–314.
23.
Reed CE, Cohen M, Enta T: Reduced effect of epinephrine on circulating eosinophils in asthma and after beta-adrenergic blockade or Bordetella pertussis vaccine. With a note on eosinopenia after methacholine. J Allergy 1970;46:90–102.
24.
Turner DJ, Myron P, Powell WS, Martin JG: The role of endogenous corticosterone in the late-phase response to allergen challenge in the brown Norway rat. Am J Respir Crit Care Med 1996;153:545–550.
25.
Buijs RM, Wortel J, Van Heerikhuize JJ, Feenstra MG, Ter Horst GJ, Romijn HJ, Kalsbeek A: Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. Eur J Neurosci 1999;11:1535–1544.
26.
Dallman MF, Engeland WC, Rose JC, Wilkinson CW, Shinsako J, Siedenburg F: Nycthemeral rhythm in adrenal responsiveness to ACTH. Am J Physiol 1978;235:R210–R218.
27.
Moore RY, Eichler VB: Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 1972;42:201–206.
28.
Cascio CS, Shinsako J, Dallman MF: The suprachiasmatic nuclei stimulate evening ACTH secretion in the rat. Brain Res 1987;423:173–178.
29.
Buijs RM, Wortel J, Van Heerikhuize JJ, Kalsbeek A: Novel environment induced inhibition of corticosterone secretion: physiological evidence for a suprachiasmatic nucleus mediated neuronal hypothalamo-adrenal cortex pathway. Brain Res 1997;758:229–236.
30.
Bartness TJ, Song CK, Demas GE: SCN efferents to peripheral tissues: implications for biological rhythms. J Biol Rhythms 2001;16:196–204.
31.
Richter HG, Torres-Farfan C, Rojas-Garcia PP, Campino C, Torrealba F, Seron-Ferre M: The circadian timing system: making sense of day/night gene expression. Biol Res 2004;37:11–28.
32.
Teixeira LK, Fonseca BP, Barboza BA, Viola JP: The role of interferon-gamma on immune and allergic responses. Mem Inst Oswaldo Cruz 2005;100(suppl 1):137–144.
33.
Lundkvist GB, Robertson B, Mhlanga JD, Rottenberg ME, Kristensson K: Expression of an oscillating interferon-gamma receptor in the suprachiasmatic nuclei. Neuroreport 1998;9:1059–1063.
34.
Clark CJ, Cochrane LM: Physical activity and asthma. Curr Opin Pulm Med 1999;5:68–75.
35.
Ram FS, Robinson SM, Black PN: Physical training for asthma. Cochrane Database Syst Rev 2000;(2):CD001116.
36.
Macris NT, Schiavi RC, Camerino MS, Stain M: Effect of hypothalamic lesions on immune processes in the guinea pig. Am J Physiol 1970;219:1205–1209.
37.
Luparello TJ, Stain M, Park CD: Effect of hypothalamic lesions on rat anaphylaxis. Am J Physiol 1964;207:911–914.
38.
Irie M, Nagata S, Endo Y: Anterior hypothalamic lesions inhibit antigen-induced airway eosinophilia in rats. Neuroimmunomodulation 2003;10:305–309.
39.
Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A: Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med 2003;198:725–736.
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2006
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