ブックタイトル教育医学 J.Educ.Health Sci.　第63巻　第3号　通巻 第289号

概要

教育医学 J.Educ.Health Sci.　第63巻　第3号　通巻 第289号

Change in Oral Antimicrobial Peptides and Neuroendocrine Response by Intense Exercisetemporal effects (kinetics of secretion over time).Recently, a variety of humoral immunemediators have been reported to participate ininnate defense mechanisms against pathogenstargeting the mucosal surface in various tissuesincluding the oral cavity and airways 19) . Inparticular, considerable evidence has been foundthat antimicrobial peptides, such as HBD-2and LL-37, play important roles in oral innateimmunity 13) . However, few studies have focusedon whether salivary levels of these novel peptidesare altered during or after exercise. Only onerecent study by Davison et al. demonstrated thatsalivary concentrations and the secretion rates ofHNP1-3 (αdefensins) and LL-37 significantlyincreased following a single bout of moderateintensity exercise 11) , suggesting the intriguingpossibility that this type of exercise might modifyantimicrobial peptide profiles in the oral secretions.However, it still remains to be elucidated whethera single bout of strenuous exercise can also affectoral antimicrobial peptide concentrations. Wefirst demonstrated a significant increase in oralHBD-2 and LL-37 levels induced by a singlebout of intense exercise. In the human oral cavity,both of these peptides were detected in salivaryglands and gingival epithelial cells 7,21,26) . Basedon in vitro studies using epithelial cultures, theproduction of HBD-2 is known to be up-regulatedby bacterial triggers and pro-inflammatorymediators, such as lipopolysaccharide (LPS),TNF-α, and IL-1β, in an NF-κB-dependentmanner 38) . Vitamin D3 and infectious triggers arerecognized as major regulators controlling LL-37 expression in humans 28) . In the setting of thepresent study, however, for only a few hourssuch infectious, proinflammatory and nutritionalfactors did not seem to stimulate directly acuteproduction of these salivary peptides. Previousstudies have demonstrated that HBD-2 and LL-37 are both expressed in normal tissues withoutinfectious and inflammatory conditions 21) , butthe precise mechanisms of the exercise-inducedtransient increases in antimicrobial peptides asobserved in the present study are unclear. Withregard to LL-37, the previous study by Davisonet al. suggested that the exercise-induced rise insalivary LL-37 levels might be attributed to localand systemic recruitment of neutrophils, whichare one of the main sources of LL-37 11) . SalivaryIgA has classically been recognized as a majoreffector of host resistance to many pathogens inthe oral cavity, and many studies have investigatedthe impact of transient or repeated exercise onits salivary levels. While some studies havereported either no change 30) or even increases 29)in salivary IgA levels, the majority of studiesdemonstrated that the concentrations in salivadeclined immediately after a single bout of intenseexercise 25) , in accordance with the present findings.The present study investigated the associationof stress markers with each oral innate immunecomponent during and after exercise. It is wellknown that physical and mental stress elicit therelease of norepinephrine from the SA axis andcortisol from the HPA axis, by which stress canmodulate various immune responses 10) . Whilebrain centers of these two stress systems innervateand stimulate each other 8) , discrepancies havebeen reported between these two hormone levelsin response to physical and psychological stressin various laboratory settings 12) , suggesting thatthese hormones seem to have different roles incoping with physical and psychological activityand recovery. In the present study, no significantassociation was found between the exerciseinducedrise in plasma norepinephrine and that insalivary cortisol levels. Of particular interest is thenegative correlation between increases in salivarycortisol levels with those in HBD-2 and LL-37 insaliva. Interestingly, previous in vitro or animalstudies have demonstrated that endogenous orexogenous glucocorticoid can down-regulatethe expression of these antimicrobial peptides invarious tissues 1) . Despite the brief time courseof the present study (1-2 hrs post-exercise? 236 ?