A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.
A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.
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DOI：
10.4049/jimmunol.159.12.6276
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发表时间：
1997-12
影响因子：
4.4
通讯作者：
S. Plevy;C. Landers;J. Prehn;N. Carramanzana;R. Deem;D. Shealy;S. Targan
中科院分区：
文献类型：
--
作者：
S. Plevy;C. Landers;J. Prehn;N. Carramanzana;R. Deem;D. Shealy;S. Targan
最近对克罗恩病患者的临床研究表明，在一次静脉内输注针对TNF-α（cA 2）的嵌合mAb后，出现了显著的临床应答。为了评估TNF-α在粘膜细胞因子调节中的作用，测定了TNF-α对固有层单核细胞（LPMC）Th 1产生的影响。在TNF-α中培养的抗CD 2刺激的LPMC中证实了IFN-γ产生的增加。为了确定cA 2对细胞因子产生的影响，在来自用cA 2治疗的5名克罗恩病患者的LPMC中定量产生TNF-α和IFN-γ的细胞。在所有4例表现出临床和内窥镜改善的患者中，在CD 2/CD 28活化后产生IFN-γ和TNF-α的LPMC数量减少导致疾病活动性在8周内改善。在一名没有改善的患者中，观察到分泌TNF-α和IFN-γ的LPMC数量增加。在四个响应患者中的三个中，CD 2/CD 28激活的PBMC表现出超过8周的IFN-γ产生增加。这些观察结果表明，TNF-α可能是粘膜Th 1应答的辅助因子，克罗恩病中cA 2诱导的临床参数和肠道炎症的改善可能通过下调粘膜Th 1细胞因子介导。
Recent clinical studies of Crohn's disease patients demonstrated dramatic clinical responses following one i.v. infusion of a chimeric mAb to TNF-alpha (cA2). To assess the role of TNF-alpha in mucosal cytokine regulation, the effects of TNF-alpha on lamina propria mononuclear cell (LPMC) Th1 production were determined. Increased IFN-gamma production was demonstrated in anti-CD2-stimulated LPMC cultured in TNF-alpha. To determine the effects of cA2 on cytokine production, TNF-alpha- and IFN-gamma-producing cells were quantitated in LPMC from five Crohn's disease patients treated with cA2. In all four patients who demonstrated clinical and endoscopic improvement, decreased numbers of LPMC producing IFN-gamma and TNF-alpha following CD2/CD28 activation paralleled improvement in disease activity over 8 wk. In one patient who did not improve, increased numbers of TNF-alpha- and IFN-gamma-secreting LPMC were observed. In three of four responding patients, CD2/CD28-activated PBMC demonstrated increased IFN-gamma production over 8 wk. These observations suggest that TNF-alpha may be a cofactor for mucosal Th1 responses, and improvement in clinical parameters and intestinal inflammation induced by cA2 in Crohn's disease may be mediated by down-regulation of mucosal Th1 cytokines.