肿瘤坏死因子α和英夫利昔单抗对感染或未感染爱泼斯坦-巴尔病毒的B淋巴细胞凋亡的影响。

Effect of tumor necrosis factor alpha and infliximab on apoptosis of B lymphocytes infected or not with Epstein-Barr virus.

作者信息

Baran-Marszak Fanny, Laguillier Christelle, Youlyouz Ibtissam, Feuillard Jean, Mariette Xavier, Fagard Remi, Raphaël Martine

机构信息

INSERM E109, CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris 11, 94275 Le Kremlin Bicêtre, France.

出版信息

Cytokine. 2006 Mar 21;33(6):337-45. doi: 10.1016/j.cyto.2006.03.005. Epub 2006 May 19.

DOI:10.1016/j.cyto.2006.03.005

PMID:16713282

Abstract

Chronic inflammation and immunosuppressive therapies increase the risk of non-Hodgkin's lymphoma associated or not with Epstein-Barr virus (EBV) infection. A possible link between infliximab treatment and increased risk of lymphoma has been suggested. Indeed, infliximab induces apoptosis of monocytes and activated T lymphocytes, but its effect on B lymphocytes infected or not with EBV is unknown. Secreted tumor necrosis factor (TNF) alpha and the expression level of TNF receptor 1 (TNFR1) and TNFR2 were compared in EBV-positive and negative B-cell lines. The impact of TNFalpha and infliximab on apoptosis of EBV-positive cells was analyzed regarding the activity of NF-kappaB. Increased expression of TNFalpha in EBV-positive cells suggested that infliximab could affect their survival. However, TNFalpha or infliximab incubation had no effect on apoptosis of EBV-positive cells. Loss of NF-kappaB activity sensitized lymphoblastoid cell lines to TNFalpha-induced apoptosis, but no direct effect of infliximab on apoptosis was detected. On the basis of our in vitro data, neither TNFalpha nor infliximab has a direct effect on apoptosis of B lymphocytes and EBV-positive cell lines. Thus, if an increased incidence of lymphoma were induced by TNFalpha blockers, it would not involve a direct effect on B cells but rather an impaired immune surveillance by T cells.

摘要

慢性炎症和免疫抑制疗法会增加非霍奇金淋巴瘤的风险，这种淋巴瘤与爱泼斯坦-巴尔病毒（EBV）感染有关或无关。已有研究表明英夫利昔单抗治疗与淋巴瘤风险增加之间可能存在联系。实际上，英夫利昔单抗可诱导单核细胞和活化T淋巴细胞凋亡，但其对感染或未感染EBV的B淋巴细胞的影响尚不清楚。对EBV阳性和阴性B细胞系中分泌的肿瘤坏死因子（TNF）α以及TNF受体1（TNFR1）和TNFR2的表达水平进行了比较。就核因子κB（NF-κB）的活性分析了TNFα和英夫利昔单抗对EBV阳性细胞凋亡的影响。EBV阳性细胞中TNFα表达增加表明英夫利昔单抗可能会影响其存活。然而，TNFα或英夫利昔单抗孵育对EBV阳性细胞的凋亡没有影响。NF-κB活性丧失使淋巴母细胞系对TNFα诱导的凋亡敏感，但未检测到英夫利昔单抗对凋亡有直接影响。根据我们的体外数据，TNFα和英夫利昔单抗对B淋巴细胞和EBV阳性细胞系的凋亡均无直接影响。因此，如果TNFα阻滞剂导致淋巴瘤发病率增加，其机制并非直接作用于B细胞，而是T细胞介导的免疫监视受损。