Atopic dermatitis: the role of recombinant interferon-gamma therapy.
Atopic dermatitis: the role of recombinant interferon-gamma therapy.
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DOI：
10.2165/00128071-200203030-00004
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发表时间：
2002-01-01
影响因子：
7.3
通讯作者：
Stevens, Seth R
中科院分区：
文献类型：
--
作者：
Chang, Timothy T;Stevens, Seth R
特应性皮炎是一种常见的、慢性的、复发性的皮肤疾病，具有典型的细胞和体液免疫异常，可导致患者显著的身体和心理疾病。特应性皮炎通常开始于儿童时期，并且通常可以持续通过青春期到成年期。虽然有多种治疗特应性皮炎的方法，但许多患者的症状没有改善或对药物有不良反应，需要寻找其他有效的治疗药物。在特应性皮炎患者中，长期以来一直注意到许多炎症和免疫学异常。虽然在理解特应性皮炎的病因方面已经取得了很大的进步，但其复杂的病理生理学仍然没有完全理解。最值得注意的是，患有特应性皮炎的患者通常具有血清免疫球蛋白（IG）E水平升高、细胞免疫抑制、血嗜酸性粒细胞增多和白细胞介素（IL）-4产生增加。此外，特应性皮炎患者的外周血单核细胞自发地和响应于刺激产生降低水平的干扰素-γ。由于这些特征，特应性皮炎最初被视为典型的2型辅助性T淋巴细胞（T（h2））疾病。这些免疫学的发现导致了一些临床试验与重组干扰素-γ的患者谁有严重的，持续的特应性皮炎。据推测，重组干扰素-γ治疗能够通过降低血清IgE水平、IL-4水平、恢复免疫平衡来纠正特应性皮炎患者的免疫失衡，从而导致临床改善。最初的开放标签研究、双盲安慰剂试验和长期开放标签研究已经证明了重组干扰素-γ在患有严重、持续性特应性皮炎的患者亚组中的临床疗效和耐受性。接受治疗的患者的临床参数的严重程度通常显著降低：红斑、水肿/硬结、瘙痒、表皮脱落、干燥、苔藓样变和相关的全身表面积受累减少。令人惊讶的是，用重组干扰素-γ治疗并没有降低血清IgE水平，这反驳了干扰素-γ将使特应性皮炎患者临床改善的假设机制。相反，观察到绝对白色血细胞和嗜酸性粒细胞计数降低，这往往与临床改善相关。尽管重组干扰素-γ在特应性皮炎患者中引起临床变化的确切机制尚不清楚，但重组干扰素-γ应被视为特应性皮炎患者的可能治疗方法。
Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical cellular and humoral immunologic abnormalities that can result in significant physical and psychological morbidity to the patient. Atopic dermatitis typically begins in childhood and can often persist through adolescence into adulthood. Although there are a variety of treatments for atopic dermatitis, many patients' symptoms do not improve or they have adverse reactions to medications, requiring the search for other, effective therapeutic agents. A number of inflammatory and immunological abnormalities have long been noted in patients with atopic dermatitis. Although great strides have been made in understanding the causes, the complex pathophysiology of atopic dermatitis is still not completely understood. Most notably, patients with atopic dermatitis often have an elevation of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated blood eosinophilia, and increased interleukin (IL)-4 production. In addition, peripheral blood mononuclear cells of patients with atopic dermatitis produce reduced levels of interferon-gamma spontaneously and in response to stimuli. Due to this constellation of features, atopic dermatitis was initially viewed as a prototypical type 2 helper T lymphocyte (T(h2)) disease. These immunological findings led to a number of clinical trials with recombinant interferon-gamma in patients who had severe, unremitting atopic dermatitis. Treatment with recombinant interferon-gamma was postulated to be able to correct the immunological imbalances in patients with atopic dermatitis by decreasing serum IgE levels, IL-4 levels, restoring immune balance, and thereby leading to clinical improvement. Initial open-label studies, a double-blind placebo trial, and long-term open-label studies have demonstrated the clinical efficacy and tolerability of recombinant interferon-gamma in a subset of patients with severe, unremitting atopic dermatitis. Patients receiving treatment often had marked decreases in severity of clinical parameters: erythema, edema/indurations, pruritus, excoriations, dryness, lichenification and associated reduction in total body surface area involvement. Surprisingly, treatment with recombinant interferon-gamma did not lower serum IgE levels refuting the hypothesized mechanism by which interferon-gamma would bring about clinical improvement in patients with atopic dermatitis. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement. Although the exact mechanism by which recombinant interferon-gamma brings about clinical changes in patients with atopic dermatitis is unknown, recombinant interferon-gamma should be considered a possible therapy for patients with atopic dermatitis.