趙廣高,蘇全生,周 石,何建偉,蘇利強(qiáng),張 瑋

(1.南昌大學(xué)體育系,江西 南昌 330031；2.成都體育學(xué)院,四川 成都 610041；3.南十字星大學(xué)健康與人體學(xué)院,澳大利亞 新南威爾士州 里斯莫爾 2480；

4.莆田學(xué)院體育學(xué)院,福建 莆田 351100；5.江西中醫(yī)藥大學(xué)體育教學(xué)部,江西 南昌 330004)

對(duì)對(duì)運(yùn)動(dòng)中機(jī)體免疫平衡評(píng)價(jià)方法的思考

趙廣高1,蘇全生2,周 石3,何建偉4,蘇利強(qiáng)5,張 瑋5

(1.南昌大學(xué)體育系,江西 南昌 330031；2.成都體育學(xué)院,四川 成都 610041；3.南十字星大學(xué)健康與人體學(xué)院,澳大利亞 新南威爾士州 里斯莫爾 2480；

4.莆田學(xué)院體育學(xué)院,福建 莆田 351100；5.江西中醫(yī)藥大學(xué)體育教學(xué)部,江西 南昌 330004)

在運(yùn)動(dòng)科學(xué)領(lǐng)域中,研究者通過(guò)測(cè)定分別產(chǎn)生IFN-γ(或IL-2)與IL-4的外周血、脾臟細(xì)胞計(jì)數(shù)(或百分比),脾臟與外周血細(xì)胞在培養(yǎng)與刺激條件下分泌Th1、Th2類細(xì)胞因子的水平,以及血液中相關(guān)細(xì)胞因子含量的方法,從細(xì)胞數(shù)量與功能上來(lái)評(píng)價(jià)運(yùn)動(dòng)中機(jī)體的免疫平衡狀態(tài)。分析認(rèn)為:(1)Th1、Th2細(xì)胞在運(yùn)動(dòng)中的變化趨勢(shì)分別與Tc1、Tc2細(xì)胞保持一致,Th1/Th2平衡能間接反映T1/T2平衡的變化。(2)相比細(xì)胞數(shù)量,細(xì)胞因子可能更能有效評(píng)價(jià)運(yùn)動(dòng)中的Th1/Th2平衡。(3)通過(guò)淋巴細(xì)胞分泌的相關(guān)細(xì)胞因子水平來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡時(shí),刺激物等實(shí)驗(yàn)條件可影響實(shí)驗(yàn)結(jié)果。(4)循環(huán)血中IFN-γ、IL-4的含量可用于間接評(píng)定運(yùn)動(dòng)中的Th1/Th2平衡。通過(guò)對(duì)運(yùn)動(dòng)中Th1/Th2平衡評(píng)價(jià)方法的分析與評(píng)述,以期為未來(lái)相關(guān)研究的設(shè)計(jì)提供依據(jù),為其成果內(nèi)容的表述提供參考。

運(yùn)動(dòng);免疫平衡;Th1/Th2平衡;T細(xì)胞;γ-干擾素;白細(xì)胞介素-4

免疫平衡狀態(tài)是反映不同人群免疫功能與健康狀況的重要評(píng)價(jià)方法。上世紀(jì)八十年代,Mosmman等[1]學(xué)者提出,輔助性T細(xì)胞(Th)可劃分為兩種功能完全不同的亞型:Th1、Th2。借助該成果,許多學(xué)者將Th1/ Th2平衡作為機(jī)體免疫平衡的評(píng)價(jià)指標(biāo)應(yīng)用于醫(yī)學(xué)領(lǐng)域的相關(guān)研究中[2-5]。之后,運(yùn)動(dòng)科學(xué)領(lǐng)域也開始出現(xiàn)采用Th1/Th2平衡評(píng)價(jià)運(yùn)動(dòng)免疫機(jī)能的研究報(bào)道[6-7]。研究過(guò)程中,學(xué)者們主要圍繞Th1與Th2細(xì)胞數(shù)量及其細(xì)胞因子水平的變化,來(lái)評(píng)價(jià)兩種類型的細(xì)胞反應(yīng)在運(yùn)動(dòng)過(guò)程中的變化。本文從基礎(chǔ)研究成果出發(fā),整理與分析了以往英文與中文學(xué)術(shù)期刊和部分學(xué)術(shù)論文中所涉及到的相關(guān)實(shí)驗(yàn)研究,對(duì)運(yùn)動(dòng)中機(jī)體Th1/Th2平衡的部分評(píng)價(jià)方法進(jìn)行了分析與思考。

1 Th1/Th2平衡及其在運(yùn)動(dòng)中的評(píng)價(jià)方法

Th細(xì)胞亞型的分類依據(jù)是分泌細(xì)胞因子的種類[1]。Th1、Th2細(xì)胞均由CD4+T細(xì)胞分化而來(lái)。Th1細(xì)胞主要分泌γ-干擾素(IFN-γ)、α-腫瘤壞死因子(TNF-α)、白細(xì)胞介素(IL)-2等,統(tǒng)稱Th1類細(xì)胞因子,其中IFN-γ為典型的Th1類細(xì)胞因子。IFN -γ等細(xì)胞因子可直接誘導(dǎo)參與呼吸爆發(fā)中酶的合成,增強(qiáng)巨噬細(xì)胞(Mφ)對(duì)吞噬體中微生物的殺傷作用。其中,IFN-γ又是主要的Mφ活化因子。Th1細(xì)胞可通過(guò)分泌的細(xì)胞因子來(lái)激活單核-巨噬細(xì)胞機(jī)能,促進(jìn)細(xì)胞介導(dǎo)的免疫應(yīng)答[8]。Th2細(xì)胞產(chǎn)生的細(xì)胞因子包括IL-4、IL-6、IL-10等,統(tǒng)稱Th2類細(xì)胞因子,其中IL-4為典型的Th2類細(xì)胞因子。這些細(xì)胞因子可促進(jìn)B細(xì)胞增殖和分化為漿細(xì)胞,產(chǎn)生抗體,引發(fā)體液免疫反應(yīng)[9]。

許多研究將Th1/Th2平衡作為機(jī)體細(xì)胞免疫和體液免疫之間平衡的評(píng)價(jià)方法[10-12]。然而,目前尚未見研究者對(duì)Th1/Th2平衡的概念進(jìn)行界定。結(jié)合基礎(chǔ)研究成果,可將Th1/Th2平衡定義為:Th1型免疫反應(yīng)與Th2型免疫反應(yīng)之間的動(dòng)態(tài)平衡變化。該變化不僅受Th1與Th2細(xì)胞數(shù)量與其所分泌細(xì)胞因子的影響,許多能產(chǎn)生相應(yīng)細(xì)胞因子的中間亞群與其他淋巴細(xì)胞也可誘發(fā)Th1/Th2平衡的變化。在運(yùn)動(dòng)科學(xué)領(lǐng)域,許多研究者分別從細(xì)胞數(shù)量與分泌功能的角度來(lái)評(píng)價(jià)Th1/Th2平衡,主要評(píng)價(jià)方法有:(1)測(cè)定分別產(chǎn)生IFN-γ(或IL-2)與IL-4的外周血、脾臟細(xì)胞計(jì)數(shù)(或百分比);(2)測(cè)定脾臟與外周血細(xì)胞在培養(yǎng)與刺激條件下分泌Th1類細(xì)胞因子IFN-γ、IL-2與Th2類細(xì)胞因子IL-4、IL-10的水平;(3)測(cè)定外周血Th1、Th2類細(xì)胞因子的含量。(表1)然而,作為Th1/Th2平衡評(píng)價(jià)的先決條件,運(yùn)動(dòng)干預(yù)下外周血、脾臟細(xì)胞中Th1與Th2細(xì)胞是否分別為細(xì)胞因子IFN-γ與IL-4的主要來(lái)源細(xì)胞?運(yùn)動(dòng)中Th1與Th2細(xì)胞數(shù)量的變化是否能有效反映Th1/Th2平衡?通過(guò)細(xì)胞因子來(lái)評(píng)價(jià)Th1/Th2平衡的兩種方法各有何特異性與關(guān)鍵點(diǎn)?研究者們并未進(jìn)行深入探討。

表1 運(yùn)動(dòng)中Th1/Th2平衡的常用評(píng)價(jià)方法

續(xù)表1

2 對(duì)運(yùn)動(dòng)中Th1/Th2平衡評(píng)價(jià)方法的思考

2.1 運(yùn)動(dòng)中Th1/Th2平衡與T1/T2平衡的關(guān)系

按照細(xì)胞的功能可將T細(xì)胞分為Th細(xì)胞和細(xì)胞毒性T細(xì)胞(Tc)等。根據(jù)不同的細(xì)胞因子分泌模式,又可將Tc細(xì)胞分為Tc1和Tc2細(xì)胞。Tc1、Tc2細(xì)胞均由CD8+T細(xì)胞分化而來(lái),兩者分泌的細(xì)胞因子類型分別和Th1、Th2細(xì)胞類似,IFN-γ和IL-4分別是兩者典型的細(xì)胞因子[31]。Th1、Tc1細(xì)胞和Th2、Tc2細(xì)胞分別組成Ⅰ型T細(xì)胞和Ⅱ型T細(xì)胞,即T1和T2細(xì)胞[32]。在相關(guān)研究中,研究者通常根據(jù)分泌的細(xì)胞因子來(lái)判斷T細(xì)胞的亞型,IFN-γ+CD4+/IL-2+CD4+和IFN-γ+CD8+/IL-2+CD8+細(xì)胞分別為Th1、Tc1細(xì)胞,IL-4+CD4+和IL-4+CD8+細(xì)胞分別為Th2與Tc2細(xì)胞,而IFN-γ+與IL-4+T細(xì)胞則分別為T1與T2細(xì)胞[33]。

T1/T2平衡是用于反映細(xì)胞免疫與體液免疫之間動(dòng)態(tài)平衡變化的重要指標(biāo)[33],Th1/Th2平衡只是T1/ T2平衡的一個(gè)組成部分。然而,文獻(xiàn)中卻常將Th1/Th2平衡作為免疫平衡的評(píng)價(jià)指標(biāo)。那么,Tc1、Tc2細(xì)胞及其分泌的細(xì)胞因子在運(yùn)動(dòng)過(guò)程中發(fā)揮作用是否可以忽略呢?實(shí)驗(yàn)研究發(fā)現(xiàn),大強(qiáng)度運(yùn)動(dòng)后外周血Tc1細(xì)胞百分比高于Th1細(xì)胞,Tc2細(xì)胞僅略低于Th2細(xì)胞;Tc1、Tc2細(xì)胞和Th1、Th2細(xì)胞分別產(chǎn)生的IFN-γ、IL-4水平較為接近[16,18],說(shuō)明Tc1/Tc2平衡在運(yùn)動(dòng)中同樣發(fā)揮了十分重要的作用。由此可見,僅用Th1/Th2平衡來(lái)評(píng)價(jià)免疫平衡具有一定的局限性。那么,運(yùn)動(dòng)過(guò)程中Th1/Th2平衡與Tc1/Tc2的變化趨勢(shì)是否具有一致性呢?相關(guān)研究結(jié)果表明,運(yùn)動(dòng)后Th1和Tc1細(xì)胞、Th2和Tc2細(xì)胞以及Th細(xì)胞和Tc細(xì)胞分泌的IFN-γ、IL-4水平的變化均保持一致[16-18]。由此可見,Th1、Th2細(xì)胞雖然只是引起細(xì)胞免疫與體液免疫的其中一類T細(xì)胞亞群,但Th1/Th2平衡仍能間接反映運(yùn)動(dòng)過(guò)程中的T1/T2平衡狀態(tài)。

2.2 運(yùn)動(dòng)中Th1、Th2細(xì)胞的數(shù)量與其功能的關(guān)系

實(shí)驗(yàn)研究中,部分學(xué)者傾向于用Th1與Th2細(xì)胞(或T1與T2細(xì)胞)數(shù)量的變化來(lái)反映運(yùn)動(dòng)中的Th1/ Th2平衡,而其他學(xué)者則更青睞于這兩類細(xì)胞所分泌細(xì)胞因子的變化,從細(xì)胞功能上來(lái)評(píng)價(jià)Th1/Th2平衡。綜合各項(xiàng)研究發(fā)現(xiàn),相似運(yùn)動(dòng)后T1、T2細(xì)胞的數(shù)量與其產(chǎn)生的細(xì)胞因子的變化趨勢(shì)并不總是保持一致[16,18,34-35],在同一實(shí)驗(yàn)研究中,大強(qiáng)度運(yùn)動(dòng)可引起循環(huán)血IFN-γ+T細(xì)胞與IL-2+T細(xì)胞水平顯著上升,但同一測(cè)試時(shí)相循環(huán)血T淋巴細(xì)胞生成的IFN-γ和IL-2水平的變化趨勢(shì)卻完全相反,呈顯著下降的趨勢(shì)[15]。以上研究提示,在評(píng)價(jià)運(yùn)動(dòng)機(jī)體Th1/Th2平衡時(shí),應(yīng)深入分析Th1、Th2細(xì)胞的數(shù)量與其產(chǎn)生細(xì)胞因子的關(guān)系。

本研究認(rèn)為,Th1、Th2類細(xì)胞因子的變化可能更能有效反映機(jī)體Th1/Th2平衡,理由如下:(1)機(jī)體的免疫反應(yīng)是由細(xì)胞因子引起,而不是由生成細(xì)胞因子的細(xì)胞引起。IFN-γ和IL-4可分別誘發(fā)Th1和Th2型免疫反應(yīng),從而介導(dǎo)細(xì)胞免疫與體液免疫,而Th1和Th2細(xì)胞卻不能直接引發(fā)相應(yīng)的免疫反應(yīng)。(2)Th1/ Th2平衡是指Th1型免疫反應(yīng)與Th2型免疫反應(yīng)之間的動(dòng)態(tài)平衡。引起Th1、Th2型免疫反應(yīng)的細(xì)胞因子并非僅由Th1、Th2細(xì)胞或T1、T2細(xì)胞生成,其他細(xì)胞也具有生成相關(guān)細(xì)胞因子的能力。Th細(xì)胞由Th0細(xì)胞分化生成,Th0細(xì)胞與其分化過(guò)程中的中間亞群均可分泌IFN-γ、IL-4等細(xì)胞因子[36]。除此之外,NK細(xì)胞等[37-38]和B細(xì)胞等[39-40]也可分別分泌IFN-γ

和IL-4等細(xì)胞因子。如果僅用Th細(xì)胞或T細(xì)胞亞群的百分比和數(shù)量來(lái)評(píng)價(jià)Th1/Th2平衡,可能就會(huì)導(dǎo)致我們由于忽視了Th0細(xì)胞、NK細(xì)胞和B細(xì)胞等的貢獻(xiàn)而產(chǎn)生偏差。(3)在運(yùn)動(dòng)前后的不同階段,機(jī)體相同數(shù)量的Th細(xì)胞分泌細(xì)胞因子的水平并不相同。在一次自行車運(yùn)動(dòng)后的30min和24h時(shí)相,單位CD4+細(xì)胞分泌的IFN-γ均顯著低于運(yùn)動(dòng)前水平[6]。Th1、Th2類細(xì)胞因子的分泌受胞內(nèi)信號(hào)傳導(dǎo)與轉(zhuǎn)錄激活因子(STAT)等轉(zhuǎn)錄因子的蛋白表達(dá)和磷酸化程度[41]等因素的影響,胞內(nèi)相關(guān)轉(zhuǎn)錄因子磷酸化程度較低的Th細(xì)胞分泌細(xì)胞因子的能力也較低。由此看來(lái),運(yùn)動(dòng)中機(jī)體Th細(xì)胞的數(shù)量和百分比并不能完全代表其相應(yīng)水平的細(xì)胞因子分泌能力,同樣也無(wú)法有效反映運(yùn)動(dòng)機(jī)體的Th1、Th2型免疫反應(yīng)和Th1/Th2平衡狀態(tài)。

2.3 通過(guò)淋巴細(xì)胞分泌的相關(guān)細(xì)胞因子水平,來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡

通過(guò)測(cè)定與分析運(yùn)動(dòng)不同時(shí)相外周血、脾臟細(xì)胞在培養(yǎng)與刺激條件下分泌Th1、Th2類細(xì)胞因子的水平,可從細(xì)胞功能上來(lái)評(píng)價(jià)運(yùn)動(dòng)過(guò)程中Th1/Th2平衡的變化。人體生理生化指標(biāo)的主要測(cè)定方法包括體內(nèi)試驗(yàn)(in vivo)、離體試驗(yàn)(ex vivo)與體外試驗(yàn)(in vitro)三種[42]。該方法屬于體外試驗(yàn)方法,相比其它兩種方法,其優(yōu)點(diǎn)在于測(cè)試指標(biāo)能更直接、更準(zhǔn)確地反映機(jī)體細(xì)胞的功能水平。然而,該方法評(píng)價(jià)效果的好壞,仍取決于對(duì)實(shí)驗(yàn)條件的控制程度。淋巴細(xì)胞在培養(yǎng)的過(guò)程中,不同刺激物和較難控制的培養(yǎng)條件都可影響實(shí)驗(yàn)結(jié)果。研究發(fā)現(xiàn),在中等強(qiáng)度與大強(qiáng)度運(yùn)動(dòng)前后的多個(gè)時(shí)相,機(jī)體外周血細(xì)胞培養(yǎng)液分別受植物血凝素(PHA)或葡萄球菌腸毒素B(SEB)刺激后,細(xì)胞產(chǎn)生IFN-γ的含量發(fā)生很大差別,且發(fā)生明顯不同的變化趨勢(shì)[6]。由此可見,刺激物的選擇對(duì)該方法的可靠性影響巨大。因此,在借助淋巴細(xì)胞分泌的相關(guān)細(xì)胞因子水平來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡的實(shí)驗(yàn)研究過(guò)程中,同時(shí)開展刺激物等實(shí)驗(yàn)條件的建立與完善方面的研究,對(duì)于實(shí)驗(yàn)本身同樣重要。

2.4 通過(guò)血液中相關(guān)細(xì)胞因子含量的變化,來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡

運(yùn)動(dòng)期間,由淋巴細(xì)胞產(chǎn)生的細(xì)胞因子通過(guò)血液循環(huán)系統(tǒng)周轉(zhuǎn)全身,從而來(lái)調(diào)節(jié)由運(yùn)動(dòng)引起的免疫功能改變[43]。運(yùn)動(dòng)過(guò)程中與運(yùn)動(dòng)結(jié)束后,淋巴細(xì)胞產(chǎn)生的Th1、Th2類細(xì)胞因子也可隨血液循環(huán)到達(dá)骨骼肌、胃腸道等免疫局部,誘發(fā)不同類型的免疫反應(yīng)。在現(xiàn)有的實(shí)驗(yàn)研究中,已有研究者通過(guò)測(cè)定循環(huán)血液中Th1、Th2類細(xì)胞因子的含量,來(lái)評(píng)價(jià)運(yùn)動(dòng)機(jī)體的Th1/Th2平衡[28-30,44]。在用該方法探討運(yùn)動(dòng)機(jī)體的Th1/ Th2平衡時(shí),需首先探討所測(cè)定細(xì)胞因子的來(lái)源細(xì)胞。其中,運(yùn)動(dòng)機(jī)體的IFN-γ主要由T細(xì)胞與NK細(xì)胞分泌;IL-4主要由Th2與Tc2細(xì)胞分泌[36]。二者主要的來(lái)源細(xì)胞均為淋巴細(xì)胞,適用于該方法。然而,運(yùn)動(dòng)期間大量的IL-6、TNF-α主要是由運(yùn)動(dòng)骨骼肌產(chǎn)生,而淋巴細(xì)胞并不是循環(huán)血中IL-6、TNF-α的主要來(lái)源細(xì)胞。由此可見,在借助血液中相關(guān)細(xì)胞因子含量來(lái)評(píng)價(jià)運(yùn)動(dòng)過(guò)程中Th1/Th2平衡的變化時(shí),應(yīng)注意對(duì)細(xì)胞因子指標(biāo)的有效選擇。

3 小結(jié)

(1)Th1、Th2細(xì)胞是引起細(xì)胞免疫與體液免疫的T細(xì)胞亞群之一,兩者在運(yùn)動(dòng)中的變化趨勢(shì)分別與Tc1、Tc2細(xì)胞保持一致,提示Th1/Th2平衡能間接反映T1/T2平衡的變化。

(2)用于間接反映運(yùn)動(dòng)機(jī)體Th1/Th2平衡狀態(tài)的T1、T2細(xì)胞數(shù)量與其產(chǎn)生細(xì)胞因子的變化趨勢(shì)并不總是保持一致。相比之下,直接用細(xì)胞因子來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡的變化可能更加有效。

(3)通過(guò)測(cè)定淋巴細(xì)胞在培養(yǎng)與刺激條件下產(chǎn)生Th1、Th2類細(xì)胞因子的水平,可從細(xì)胞功能上來(lái)評(píng)價(jià)運(yùn)動(dòng)中Th1/Th2平衡的變化,但刺激物等實(shí)驗(yàn)條件對(duì)實(shí)驗(yàn)結(jié)果的影響較大。

(4)循環(huán)血中IFN-γ、IL-4的含量可用于間接評(píng)定運(yùn)動(dòng)中的Th1/Th2平衡。

[1]Mosmann TR,Cherwinski H,Bond MW,et al.Two types of murine helper T cell clone.I.Definition according to profiles of lymphokine activities and secreted proteins[J].Journal of Immunology,1986,136(7):2348-2357.

[2]Chang X,Fu Y,Zhang Y,et al.Effects of Th1 and Th2 cells balance in pulmonary injury induced by nano titanium dioxide[J]. Environmental Toxicology&Pharmacology,2014,37(1):275-283.

[3]Begg DJ,de Silva K,Carter N,et al.Does a Th1 over Th2 dominancy really exist in the early stages of Mycobacterium avium subspecies paratuberculosis infections[J].Immunobiology,2011, 216(7):840-846.

[4]Gu X,Li P,Liu H,et al.The effect of influenza virus A on th1/th2 balance and alveolar fluid clearance in pregnant rats[J]. Experimental Lung Research,2011,37(7):445-451.

[5]Ekman B,Alstrand N,Bachrach-Lindstr¨om M,et al.Altered chemokine th1/th2 balance in addison's disease:relationship with hydrocortisone dosing and quality of life[J].Hormone& Metabolic Research,2014,46(1):48-53.

[6]Baum M,Müller-Steinhardt M,Liesen H,et al.Moderate and exhaustive endurance exercise influences the interferon-gamma levels in whole-blood culture supernatants[J].European Journal of Applied Physiology and Occupational Physiology,1997, 76(2):165-169.

[7]洪長(zhǎng)清.大負(fù)荷力量訓(xùn)練中機(jī)體細(xì)胞和分子免疫變化規(guī)律的研究[D].北京體育大學(xué)博士論文,2005.

[8]Sch¨affer M,Barbul A.Lymphocyte function in wound healing and following injury[J].The British Journal of Surgery,1998,85 (4):444-460.

[9]Gor DO,Rose NR,Greenspan NS.TH1-TH2:a procrustean paradigm[J].Nature Immunology,2003,4(6):503-505.

[10]Maeyama J,Takatsuka H,Iho S,et al.A palindromic CpG -containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated TH1 immunity[J].Plos ONE,2014,9(2):1-10.

[11]Libetta C,Esposito P,Sepe V,etal.Effects of different peritoneal dialysis fluids on the TH1/TH2 balance[J].European Cytokine Network,2011,22(1):24-31.

[12]Hoepner S,Loh J,Walker P,et al.Synergy between CD8 T cells and Th1 or Th2 polarised CD4 T cells for adoptive immunotherapy of brain tumours[J].Plos ONE,2013,8(5):1-9.

[13]楊斌,黃立新,何敏,等.谷氨酰胺對(duì)運(yùn)動(dòng)員Th1/Th2細(xì)胞平衡影響的研究[J].現(xiàn)代預(yù)防醫(yī)學(xué),2012,39(3):569-571.

[14]Shimizu K,Kimura F,Akimoto T,et al.Effect ofmoderate exercise training on T-helper cell subpopulations in elderly people [J].Exercise Immunology Review,2008,14:24-37.

[15]Starkie RL,Rolland J,Febbraio MA.Effect of adrenergic blockade on lymphocyte cytokine production at restand during exercise[J].American Journal of Physiology Cell Physiology,2001, 281(4):1233-1240.

[16]Ibfelt T,Petersen EW,Bruunsgaard H,et al.Exercise-induced change in type 1 cytokine-producing CD8+T cells is related to a decrease in memory T cells[J].Journal of Applied Physiology,2002,93(2):645-648.

[17]Steensberg A,Toft AD,Bruunsgaard H,etal.Strenuous exercise decreases the percentage of type 1 T cells in the circulation [J].Journal of Applied Physiology,2001,91(4):1708-1712.

[18]Lancaster GI,Khan Q,Drysdale PT,et al.Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans[J].Journal of Applied Physiology,2005,98(2):565-571.

[19]Kapasi ZF,McRae ML,Ahmed R.Suppression of viral specific primary T-cell response following intense physical exercise in young but not old mice[J].Journal of Applied Physiology,2005, 98(2):663-671.

[20]KohutML,Boehm GW,Moynihan JA.Moderate exercise is associated with enhanced antigen-specific cytokine,but not IgM antibody production in aged mice[J].Mechanisms of Ageing and Development,2001,122(11):1135-1150.

[21]Kohut ML,Thompson JR,Lee W,et al.Exercise traininginduced adaptations of immune response aremediated by beta-adrenergic receptors in aged but not youngmice[J].Journal of Applied Physiology,2004,96(4):1312-1322.

[22]KohutML,Martin AE,Senchina DS,et al.Glucocorticoids produced during exercise may be necessary for optimal virus-induced IL-2 and cell proliferation whereas both catecholamines and glucocorticoidsmay be required for adequate immune defense to viral infection[J].Brain,Behavior,and Immunity,2005,19(5): 423-435.

[23]Wang R,Chen P.Modulation of NKT cells and Th1/Th2 imbalance after alpha-GalCer treatment in progressive load-trained rats[J].International Journal of Biological Sciences,2009,5 (4):338-343.

[24]何偉,陳靜寧.下坡蛙跳運(yùn)動(dòng)對(duì)Th1/Th2偏移的影響與Cor,IL-1β和IL-6的關(guān)系[J].北京體育大學(xué)學(xué)報(bào),2011, 34(5):63-65.

[25]劉靜,陳佩杰,王茹.太極拳運(yùn)動(dòng)對(duì)中老年女性外周血白細(xì)胞細(xì)胞因子IFN-γ、IL-4的影響[J].中國(guó)運(yùn)動(dòng)醫(yī)學(xué)雜志, 2009,28(5):557-558.

[26]曲靜,王曉慧,婁淑杰.運(yùn)動(dòng)性免疫抑制大鼠肝,脾糖皮質(zhì)激素受體表達(dá)變化探討[J].中國(guó)運(yùn)動(dòng)醫(yī)學(xué)雜志,2012,31 (8):710-716.

[27]Gray P,Gabriel B,Thies F,et al.Fish oil supplementation augments post-exercise immune function in young males[J]. Brain,Behavior,and Immunity,2012,26:1265-1272.

[28]Wang JS,Chen WL,Weng TP.Hypoxic exercise training reduces senescent T-lymphocyte subsets in blood[J].Brain,Behavior,and Immunity,2011,25(2):270-278.

[29]蘇利強(qiáng),張利明,張瑋,等.不同負(fù)荷運(yùn)動(dòng)對(duì)大鼠Th1/ Th2平衡及脾淋巴細(xì)胞PKC活性的影響[J].沈陽(yáng)體育學(xué)院學(xué)報(bào),2011,30(5):64-68.

[30]徐唯.不同負(fù)荷運(yùn)動(dòng)對(duì)急性心理應(yīng)激大鼠Th1/Th2平衡的影響[J].現(xiàn)代預(yù)防醫(yī)學(xué),2013,40(2):333-335.

[31]Gulzar N,Diker B,Balasubramanian S,etal.Human immunodeficiency virus-1 infection protects against a Tc1-to-Tc2 shift in CD8+T cells[J].Human Immunology,2011,72(11): 995-1000.

[32]趙武述.免疫平衡研究及其臨床意義[M].北京:科學(xué)出版社,2005.

[33]Zhao G,Zhou S,Davie A,etal.Effects ofmoderate and high intensity exercise on T1/T2 balance[J].Exercise Immunology Review,2012,18:98-114.

[34]Lancaster GI,Halson SL,Khan Q,et al.Effects of acute exhaustive exercise and chronic exercise training on type 1 and type 2 T lymphocytes[J].Exercise Immunology Review,2004,10:91 -106.

[35]Sellar CM,Syrotuik DG,Field CJ,et al.The effectof dietary control and carbohydrate supplementation on the immune and hormonal responses to rowing exercise[J].Applied Physiology, Nutrition,and Metabolism,2006,31(5):588-596.

[36]Kushwah R,Gagnon S,Sweezey N.Intrinsic predisposition of na¨ive cystic fibrosis T cells to differentiate towards a Th17 phenotype[J].Respiratory Research,2013,14(12):1-8.

[37]Aravena O,Pesce B,Soto L,et al.Anti-TNF therapy in patientswith rheumatoid arthritis decreases Th1 and Th17 cell populations and expands IFN-γ-producing NK cell and regulatory T cell subsets[J].Immunobiology,2011,216(12):1256-1263.

[38]Kannan Y,Yu J,Raices RM,et al.IκBζaugments IL-12 -and IL-18-mediated IFN-γproduction in human NK cells [J].Blood,2011,117(10):2855-2863.

[39]Harris DP,Goodrich S,Mohrs K,et al.Cutting edge:the development of IL-4-producing B cells(B effector 2 cells)is controlled by IL-4,IL-4 receptor alpha,and Th2 cells[J]. Journal of Immunology,2005,175(11):7103-7107.

[40]Smith N,Tierney R,Rowe M,et al.Induction of Interferon -stimulated genes on the IL-4 response axis by epstein-barr virus infected human B cells;relevance to cellular transformation [J].Plos ONE,2013,8(5):1-13.

[41]Rengarajan J,Szabo SJ,Glimcher LH.Transcriptional regulation of Th1/Th2 polarization[J].Immunology Today,2000,21 (10):479-483.

[42]Balkwill F.The cytokines network[M].Oxford:Oxford University Press,2000.

[43]Suzuki K,Yamada M,Kurakake S,et al.Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans[J].European Journal of Applied Physiology,2000,81(4):281-287.

[44]蘇利強(qiáng),張瑋,趙廣高,等.PKC在運(yùn)動(dòng)性免疫抑制發(fā)生過(guò)程中的作用[J].上海體育學(xué)院學(xué)報(bào),2011,35(3):56-59.

Reflection on the Evaluation M ethod of Immune Balance in Exercise

ZHAO Guanggao,et al
(Nanchang University,Nanchang Jiangxi,330031)

In the field of sports science,the number/percentage of IFN-γ(or IL-2)and IL-4 cells in peripheral blood or spleen,the levels of Th1,Th2-associated cytokines produced by the cells,and the concentrations of the cytokines in circulation are measured by researchers to evaluate the Th1/Th2 balance following exercise from the perspective of Th1and Th2 cell numbers and function.The analysis believes that(1)The change of Th1 and Th2 cells in response to exercise is the same as that of Tc1 and Tc2 cells respectively,while Th1/Th2 balance can be used as the indicator of T1/T2 balance indirectly.(2)The concentration of cytokinesmay be themoremeaningful indicators of Th1/ Th2 balance in response to exercise than that of cell numbers.(3)The concentration of cytokines in the circulationmay be themoremeaningful indicators of Th1/Th2 balance in response to exercise than that of cytokines produced by lymphocytes.The review is to provide the basis for study protocols and reference for discussions in the future researches through the reflection on the evaluation of Th1/Th2 balance in response to exercise.

exercise;immune balance;Th1/Th2 balance;T cells;IFN-γ;IL-4

G804

:A

:1001-9154(2014)12-0079-06

G804

:A

:1001-9154(2014)12-0079-06

江西省自然科學(xué)基金項(xiàng)目(2011ZBAB204028)。

趙廣高(1982-),男,河南周口人,副教授,博士,研究方向:運(yùn)動(dòng)生理學(xué)。通訊作者:蘇全生。

2014-05-22