Allen Shannon Sedberry, Cassone Lynne, Lasco Todd M, McMurray David N
Department of Medical Microbiology & Immunology, Texas A&M University System Health Science Center, College Station, Texas 77843, USA.
Infect Immun. 2004 Mar;72(3):1358-63. doi: 10.1128/IAI.72.3.1358-1363.2004.
Transforming growth factor beta (TGF-beta) is a cytokine which has been shown to suppress the antimycobacterial immune responses of humans and experimental animals. In this study, the contributions of TGF-beta to cytokine production in vivo were investigated by using the established guinea pig model of tuberculous pleurisy. Mycobacterium bovis BCG-vaccinated guinea pigs were injected intrapleurally with heat-killed virulent Mycobacterium tuberculosis. Eight days following induction of an antigen-specific pleural effusion, guinea pigs were injected intrapleurally with anti-TGF-beta1 or isotype control antibody. The following day, pleural exudates were removed, and the fluid volume and characteristics of the infiltrating cells were determined. Pleural fluid was analyzed for total interferon (IFN) and tumor necrosis factor (TNF) protein levels by using appropriate bioassays. RNA from pleural effusion cells was examined to determine TGF-beta1, TNF-alpha, IFN-gamma, and interleukin-8 mRNA levels by using real-time PCR. Proliferative responses of pleural effusion lymphocytes were examined in response to concanavalin A and purified protein derivative (PPD) in vitro. Treatment with anti-TGF-beta1 resulted in decreased pleural fluid volume and decreased cell numbers in the pleural space along with an increased percentage of lymphocytes and a decreased percentage of neutrophils. The bioactive TNF protein levels in pleural fluid were increased in guinea pigs treated with anti-TGF-beta1, while the bioactive IFN protein concentrations were not altered. Expression of TGF-beta1 and TNF-alpha mRNA was significantly increased following TGF-beta1 neutralization. Finally, PPD-induced proliferative responses of pleural cells from anti-TGF-beta1-treated animals were significantly enhanced. Thus, TGF-beta1 may be involved in the resolution of this local, mycobacterial antigen-specific inflammatory response.
转化生长因子β（TGF-β）是一种细胞因子，已被证明可抑制人类和实验动物的抗分枝杆菌免疫反应。在本研究中，通过使用已建立的结核性胸膜炎豚鼠模型，研究了TGF-β对体内细胞因子产生的作用。用牛分枝杆菌卡介苗接种的豚鼠经胸膜内注射热灭活的强毒结核分枝杆菌。在诱导抗原特异性胸腔积液8天后，给豚鼠胸膜内注射抗TGF-β1或同型对照抗体。次日，抽取胸腔渗出液，测定液体体积和浸润细胞的特征。通过适当的生物测定法分析胸腔积液中的总干扰素（IFN）和肿瘤坏死因子（TNF）蛋白水平。使用实时PCR检测胸腔积液细胞的RNA，以确定TGF-β1、TNF-α、IFN-γ和白细胞介素-8的mRNA水平。体外检测胸腔积液淋巴细胞对刀豆球蛋白A和纯化蛋白衍生物（PPD）的增殖反应。用抗TGF-β1治疗导致胸腔积液体积减少，胸腔内细胞数量减少，同时淋巴细胞百分比增加，中性粒细胞百分比降低。用抗TGF-β1治疗的豚鼠胸腔积液中生物活性TNF蛋白水平升高，而生物活性IFN蛋白浓度未改变。TGF-β1中和后，TGF-β1和TNF-α mRNA的表达显著增加。最后，抗TGF-β1治疗动物的PPD诱导的胸腔细胞增殖反应显著增强。因此，TGF-β1可能参与了这种局部的、分枝杆菌抗原特异性炎症反应的消退。
