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 Exercisethat collectively create a first-line mucosal barrieragainst irritants 14) . Oral surface fluid substanceswith antimicrobial activity are important humoralelements in the innate immune system. In recentyears, a novel class of antimicrobial peptides,such as defensins and cathelicidins, has emergedas a potential player in host defenses at the oralmucosal surface 16,19) . These peptides have abroad spectrum of properties against pathogens,including bacteria, fungi, and viruses 13) .Defensins are cationic peptides that contain sixcysteines forming three intramolecular disulfidebridges, and can be divided into the followingcategories:α-defensins (human neutrophilpeptides: HNP1-3),β-defensins (HBD-1 toHBD-4), andθ-defensins 16) . HBD-2 is expressedin human epithelial cells of the inner and outersurfaces of the human body, including the oralcavity and respiratory tracts 13) . LL-37 is the onlymember of the cathelicidin family in humans 28)that is produced by epithelial cells, macrophages,and neutrophils and secreted into the oral andairway surface fluids 28) . While expression ofsome antimicrobial peptides 32) is known to be upregulatedwhen active inflammation and infectionis present in various mucosal tissues, it has notbeen fully investigated whether other intrinsic andextrinsic factors, such as exercise associated withphysical stress, could also promote or inhibit theproduction of these peptides.The stress system includes brain nuclei, such asthe paraventricular nucleus of the hypothalamusand the locus ceruleus, and two powerful peripheralneuroendocrine limbs, the hypothalamuspituitary-adrenal(HPA) axis and the sympatheticand adrenomedullary (SA) systems 9) . While serumand saliva cortisol levels represent HPA axisadaptation to stress, the plasma norepinephrinelevel is thought to be a reliable measure ofactivity in the SA pathway. These parametersare classically used as biomarkers of mental andphysical stress. Practical applications includeobservation of changes in these parameters duringvarious types of exercise 22) . Recent studies haveshown a complex interplay between these twopathways in various conditions 9) . However, theassociation of changes in each stress parameterwith those in oral immunological compounds isstill unclear.We hypothesized that the amount ofantimicrobial peptides in the oral cavity mightbe affected by exercise-induced physical stress,and that the two main neuroendocrinologicalresponses to exercise, the HPA axis and SAactivity, might be differentially or synergisticallyassociated with these immunological changes.To test this hypothesis, we observed time coursechanges in the saliva levels of HBD-2, LL-37,and IgA with those in physical stress markers ofthe HPA axis (salivary cortisol) and SA activity(plasma norepinephrine levels) during a singlebout of strenuous exercise in young adult subjects.Ⅱ．Method1. SubjectsSeven young male university students (mean±SD: age 23±3yr; height 175.4±3.0cm; bodymass 69.8±6.8kg; V・O 2 max 48.7±4.8 ml/kg/min) volunteered to participate in the presentstudy. All subjects reported as 1) being activein recreational sport and physical activity courses,but having never participated in any trainingfor any particular sports, 2) being life-long nonsmokers20) , 3) not having a history of respiratoryand allergic diseases, including asthma, rhinitis,and eczema 4) , 4) not having psychological diseasesnor having experienced any significant lifeevents, such as death, accident, or divorce in familywithin the previous 6 months 35) . Subjects whohad a respiratory infection, a dental problem, orany medications within 4 weeks prior to the studywere excluded because these conditions might affectthe baseline secretion of immunological peptidesin the oral cavity 36) . All subjects providedwritten informed consent for participation in the? 228 ?