Department of Pediatric Gastroenterology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
Inflamm Bowel Dis. 2010 May;16(5):856-69. doi: 10.1002/ibd.21132.
Systemic exposure to lipopolysaccharide (LPS) has been linked to clinical disease activity in adults with inflammatory bowel disease (IBD). We hypothesized that markers of LPS exposure and the acute phase response (APR) would be increased in pediatric IBD patients with growth failure, and that LPS signaling would be required for induction of the APR in murine colitis.
Serum markers of LPS exposure, endotoxin core IgA antibody (EndoCAb), and the APR, LPS binding protein (LBP) were quantified in pediatric IBD patients and controls. LBP and cytokine production were determined after administration of trinitrobenzene sulfonic acid (TNBS) enemas to mice with genetic deletion of Toll-Like receptor 4 (TLR4), and wildtype (WT) controls.
Serum EndoCAb and LBP were significantly elevated in patients with Crohn's disease (CD), compared to disease controls with ulcerative colitis (UC) and healthy controls (P < 0.001). This was independent of disease activity or location. CD patients with elevated serum EndoCAb and LBP exhibited linear growth failure which persisted during therapy. Serum LBP increased in WT mice following TNBS administration, in conjunction with increased serum TNF-alpha, IL-6, and IL-10, and expansion of regulatory T-cell numbers. Both the APR and expansion of foxp3+ T cells were abrogated in TLR4-deficient mice, in conjunction with a reduction in acute weight loss.
LPS exposure and a persistent APR are associated with growth failure in pediatric CD. LPS signaling is required for the APR in murine colitis. Therapies targeting this pathway may benefit the subset of patients with refractory growth failure.
脂多糖（LPS）的全身暴露与成人炎症性肠病（IBD）的临床疾病活动有关。我们假设，生长不良的儿科 IBD 患者的 LPS 暴露和急性期反应（APR）标志物会增加，并且 LPS 信号传导对于诱导鼠结肠炎中的 APR 是必需的。
在儿科 IBD 患者和对照组中定量测定 LPS 暴露标志物、内毒素核心 IgA 抗体（EndoCAb）和 APR、LPS 结合蛋白（LBP）。在基因缺失 Toll 样受体 4（TLR4）的小鼠和野生型（WT）对照中，给予三硝基苯磺酸（TNBS）灌肠后，测定 LBP 和细胞因子的产生。
与溃疡性结肠炎（UC）疾病对照和健康对照相比，克罗恩病（CD）患者的血清 EndoCAb 和 LBP 显着升高（P <0.001）。这与疾病活动或位置无关。血清 EndoCAb 和 LBP 升高的 CD 患者表现出线性生长不良，在治疗期间持续存在。WT 小鼠在 TNBS 给药后血清 LBP 增加，同时血清 TNF-α、IL-6 和 IL-10 增加，调节性 T 细胞数量增加。TLR4 缺陷型小鼠中的 APR 和 foxp3+T 细胞的扩增均被阻断，同时急性体重减轻减少。
LPS 暴露和持续的 APR 与儿科 CD 患者的生长不良有关。LPS 信号传导对于鼠结肠炎中的 APR 是必需的。针对该途径的治疗方法可能对难治性生长不良的患者亚组有益。
