Tron V A, Rosenthal D, Sauder D N
Department of Medicine, McMaster University, Ontario, Canada.
J Invest Dermatol. 1988 Mar;90(3):378-81. doi: 10.1111/1523-1747.ep12456433.
Interleukin-1 (IL-1) is a monocyte-derived polypeptide with immunoregulatory and proinflammatory functions. Although monocytes are the principle source of IL-1, other cells, such as keratinocytes, endothelial cells, renal mesangial cells, and neutrophils, produce a factor with IL-1 activity. The IL-1-like polypeptide produced by keratinocytes, epidermal-derived thymocyte-activating factor (ETAF), is similar on biological, biochemical, and molecular levels to monocyte-derived IL-1. Studies of IL-1 or ETAF have for the most part been undertaken using cell culture supernatants or cell lysates, and in situ localization of ETAF has not been demonstrated. Previous studies have suggested that ETAF is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL). To gain insights into the role of these cytokines in disease states, we investigated whether IL-1 could be localized in tissue sections using a direct immunofluorescence technique with a monoclonal antibody directed against IL-1. This monoclonal antibody partially inhibited ETAF activity and totally inhibited IL-1 activity in the co-stimulator assay and so could be used to detect IL-1 or ETAF. We studied skin biopsies from 10 healthy individuals, 10 patients with CTCL, and 11 patients with various inflammatory dermatoses. Intense epidermal fluorescence was demonstrated in all cases of CTCL, whereas minimal reactivity was visible in normal biopsies and the inflammatory dermatoses. Most patients with CTCL showed an intercellular pattern, while none of the normal controls or those with inflammatory dermatoses showed this pattern. An irrelevant IgM monoclonal antibody, used as a negative control, did not demonstrate epidermal staining. To further demonstrate specificity, we incubated the anti-IL-1 antibody with recombinant beta IL-1:Epidermal reactivity was completely blocked. In a separate experiment, COLO 16 cells, a squamous cell carcinoma cell line that constitutively produces ETAF, stained positively for the IL-1 antibody. We conclude that epidermal IL-1 is elevated in CTCL.
白细胞介素-1（IL-1）是一种由单核细胞产生的具有免疫调节和促炎功能的多肽。虽然单核细胞是IL-1的主要来源，但其他细胞，如角质形成细胞、内皮细胞、肾系膜细胞和中性粒细胞，也能产生具有IL-1活性的因子。角质形成细胞产生的IL-1样多肽，即表皮衍生的胸腺细胞激活因子（ETAF），在生物学、生物化学和分子水平上与单核细胞衍生的IL-1相似。对IL-1或ETAF的研究大多是使用细胞培养上清液或细胞裂解物进行的，ETAF的原位定位尚未得到证实。先前的研究表明，ETAF参与皮肤T细胞淋巴瘤（CTCL）的发病机制。为了深入了解这些细胞因子在疾病状态中的作用，我们使用针对IL-1的单克隆抗体，通过直接免疫荧光技术研究了IL-1是否可以在组织切片中定位。在共刺激试验中，这种单克隆抗体部分抑制ETAF活性并完全抑制IL-1活性，因此可用于检测IL-1或ETAF。我们研究了10名健康个体、10名CTCL患者和11名患有各种炎症性皮肤病患者的皮肤活检样本。在所有CTCL病例中均显示出强烈的表皮荧光，而在正常活检样本和炎症性皮肤病样本中可见的反应性极小。大多数CTCL患者表现出细胞间模式，而正常对照组或患有炎症性皮肤病的患者均未表现出这种模式。用作阴性对照的无关IgM单克隆抗体未显示表皮染色。为了进一步证明特异性，我们将抗IL-1抗体与重组β IL-1一起孵育：表皮反应性被完全阻断。在另一个实验中，COLO 16细胞，一种组成性产生ETAF的鳞状细胞癌细胞系，对IL-1抗体呈阳性染色。我们得出结论，CTCL中表皮IL-1升高。
