Bonifati C, Mussi A, D'Auria L, Carducci M, Trento E, Cordiali-Fei P, Ameglio F
Department of Dermatology, Istitute S. Gallicano, IRCCS, Rome, Italy.
Arch Dermatol Res. 1998 Jan-Feb;290(1-2):9-13. doi: 10.1007/s004030050269.
Several cytokines are increased in psoriatic skin, mainly at the lesional level. Some of these mediators seem to be very important in the pathogenesis of psoriasis since they are thought to stimulate keratinocyte proliferation and/or to drive the inflammatory changes associated with psoriasis. Among the proinflammatory modulators, hematopoietins, which are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. The hematopoietin family includes interleukin-6 (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have been found to be increased in psoriatic lesions. The present study adds new information concerning the spontaneous release of two hematopoietins, namely LIF and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using commercially available ELISA kits. The results are expressed as picograms per milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, range under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken together with the fact that at least two other hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietins in inflammatory processes associated with psoriasis.
多种细胞因子在银屑病皮肤中增加，主要是在皮损部位。其中一些介质在银屑病发病机制中似乎非常重要，因为它们被认为可刺激角质形成细胞增殖和/或引发与银屑病相关的炎症变化。在促炎调节剂中，血细胞生成素是一类共享受体成分（gp130亚基）的细胞因子家族，近年来受到了深入研究。血细胞生成素家族包括白细胞介素-6（IL-6）、白细胞介素-11（IL-11）、白血病抑制因子（LIF）、抑瘤素-M（OSM）、粒细胞集落刺激因子（G-CSF）、睫状神经营养因子（CNTF）和心肌营养素。已发现其中两种分子IL-6和IL-11在银屑病皮损中的含量增加。本研究提供了关于银屑病患者和正常受试者皮损及非皮损皮肤打孔活检组织48小时培养上清液中两种血细胞生成素即LIF和OSM自发释放的新信息。使用市售ELISA试剂盒进行细胞因子测定。结果以每毫克组织皮克数表示，经过重量归一化处理。皮损皮肤释放的LIF水平（中位数2.4 pg/mg，范围0.05 - 13.4 pg/mg）显著高于非皮损皮肤（中位数0.4 pg/mg，范围低于检测限（UDL）- 4.4 pg/mg；P = 0.001）和正常皮肤（中位数0.4 pg/mg，范围UDL - 0.9 pg/mg；P = 0.005）。OSM水平在皮损皮肤上清液中（中位数0.9 pg/mg，范围0.4 - 5.2 pg/mg）也显著高于非皮损皮肤上清液（中位数0.2 pg/mg，范围UDL - 0.8 pg/mg；P = 0.001）和正常皮肤上清液（中位数0.1 pg/mg，范围UDL - 0.4 pg/mg；P = 0.0001）。此外,白细胞介素-8（IL-8）是一种参与银屑病发病机制的细胞因子，在相同样本中检测时表现出类似的情况。皮损皮肤的中位数为752.5 pg/mg，范围98.8 - 2063.8 pg/mg，非皮损皮肤的中位数为58.3 pg/mg，范围UDL - 1252.5 pg/mg（P = 0.007），正常皮肤的中位数为44.6 pg/mg，范围UDL - 176.7 pg/mg（P = 0.004）。对于所分析的三种分子，非皮损皮肤和正常皮肤之间未发现显著差异。结合至少另外两种血细胞生成素（即IL-6和IL-11）在银屑病皮损上清液中也增加这一事实，这些数据表明血细胞生成素可能参与了与银屑病相关的炎症过程。
