Fudala Rafal, Krupa Agnieszka, Stankowska Dorota, Allen Timothy C, Kurdowska Anna K
Department of Biochemistry, University of Texas Health Center, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Clin Sci (Lond). 2008 Mar;114(6):403-12. doi: 10.1042/CS20070272.
ALI/ARDS (acute lung injury/acute respiratory distress syndrome) is a severe inflammatory lung disease associated with very high mortality. Importantly, no effective therapy has been developed to date for ALI/ARDS. Neutrophils have been implicated in the pathogenesis of ALI/ARDS, and IL-8 (interleukin-8) has been identified as the main chemotactic factor for neutrophils in lung fluids of patients with ALI/ARDS. Significantly, studies from our laboratory have revealed the presence of anti-IL-8 autoantibody:IL-8 immune complexes in lung fluids from patients with ALI/ARDS. Autoantibodies to several cytokines, including IL-8, have been found in human plasma and other tissues. The function of anticytokine autoantibodies is far from clear; however, in some instances, it has been suggested that such autoantibodies may contribute to the pathogenesis of variety of human diseases. In addition, many of these autoantibodies can form immune complexes with target cytokines. Furthermore, immune complexes consisting of anti-IL-8 autoantibodies and IL-8 are very stable due to the high affinity of autoantibodies against IL-8. These complexes are present in various human tissues, including the lung, as they have been detected in lung fluids from patients with ALI/ARDS. In this review, the significance of the latter findings are explored, and the possible involvement of anti-IL-8 autoantibody:IL-8 immune complexes in pathogenesis of ALI/ARDS is discussed.
急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是一种严重的炎症性肺部疾病,死亡率极高。重要的是,迄今为止尚未开发出针对ALI/ARDS的有效治疗方法。中性粒细胞与ALI/ARDS的发病机制有关,白细胞介素-8(IL-8)已被确定为ALI/ARDS患者肺液中中性粒细胞的主要趋化因子。值得注意的是,我们实验室的研究发现,ALI/ARDS患者的肺液中存在抗IL-8自身抗体:IL-8免疫复合物。在人血浆和其他组织中已发现针对包括IL-8在内的多种细胞因子的自身抗体。抗细胞因子自身抗体的功能尚不清楚;然而,在某些情况下,有人认为这种自身抗体可能参与多种人类疾病的发病机制。此外,许多这些自身抗体可与靶细胞因子形成免疫复合物。此外,由于自身抗体对IL-8的高亲和力,由抗IL-8自身抗体和IL-8组成的免疫复合物非常稳定。这些复合物存在于包括肺在内的各种人体组织中,因为它们已在ALI/ARDS患者的肺液中被检测到。在这篇综述中,探讨了后一发现的意义,并讨论了抗IL-8自身抗体:IL-8免疫复合物可能参与ALI/ARDS发病机制的情况。