Prens E P, Benne K, van Damme J, Bakkus M, Brakel K, Benner R, van Joost T
Department of Dermatology, University Hospital Rotterdam-Dijkzigt, Erasmus University Rotterdam, The Netherlands.
J Invest Dermatol. 1990 Dec;95(6 Suppl):121S-124S. doi: 10.1111/1523-1747.ep12874991.
We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients. Different approaches were pursued. Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay. Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies. Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin. Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta. Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable. Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients. In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced "dot-like" intracellular staining pattern was observed. On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions. Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line. Very low levels of IL-6 mRNA were expressed in KC from psoriasis lesions and healthy individuals. Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA. The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL-1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells. This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales. Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA. dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo.
我们报告了银屑病患者皮肤中白细胞介素-1（IL-1）和白细胞介素-6（IL-6）的表达水平。我们采用了不同的方法。最初，使用灵敏的酶联免疫吸附测定法（ELISA）和生物测定法，检测了银屑病患者皮损处和非皮损处皮肤的抽吸疱液中IL-1β和IL-6的水平。还使用IL-1β和IL-6特异性抗体检查了皮肤切片中IL-1和IL-6的存在情况。最后，测定了银屑病皮肤培养的角质形成细胞（KC）和成纤维细胞中IL-1和IL-6 mRNA的表达。银屑病皮损处和非皮损处皮肤以及健康个体皮肤的抽吸疱液中均未检测到可检测水平（大于100 pg/ml）的IL-1β。银屑病皮损处的疱液中IL-6含量较低但具有显著意义，而这些患者的血清中IL-6水平无法检测到。在间接免疫过氧化物酶技术中，使用冷冻切片和IL-1β特异性单克隆抗体（MoAb），在银屑病患者非皮损处皮肤切片中观察到整个表皮有弥漫性染色。在银屑病皮损的冷冻切片中，观察到表皮有微弱的弥漫性染色和明显的“点状”细胞内染色模式。另一方面，在使用未固定表皮细胞的间接免疫荧光技术中，相同的IL-1β特异性MoAb在银屑病皮损的表皮细胞悬液中显示出明亮的膜染色。与正常KC和HEp-2细胞系相比，银屑病皮损处培养的KC中IL-1β和IL-1α mRNA水平略有升高。银屑病皮损处和健康个体的KC中IL-6 mRNA表达水平极低。银屑病皮损处的成纤维细胞表达极低水平的IL-1α和IL-1β，但IL-6 mRNA水平较高。结果表明银屑病皮肤存在一种矛盾的情况：银屑病皮损处的疱液中不含IL-1β，而IL-1β在表皮细胞的质膜和细胞内区室中过度表达。这一发现可能有助于解释在银屑病鳞屑水提取物中观察到的IL-1缺失现象。由于银屑病皮损处培养的KC表达极低水平的IL-6 mRNA，真皮成纤维细胞可能与炎症浸润一起，在体内代表了银屑病皮损中IL-6的主要来源。
