Interleukin-8. Differential expression in lone fibrosing alveolitis and systemic sclerosis.

Abstract

Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and compared it with that in normal individuals and sarcoidosis and systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8 protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and IL-8 mRNA expression was assessed using Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of lung parenchyma. Compared with normal subjects, IL-8 concentration was significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA expression evaluated by Northern analysis was seen only in patients with CFA and FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8 within the lower respiratory tract.

Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis

“…Interleukin-8, a chemokine produced primarily by cells of the monocyte/macrophage lineage, is a potent and selective chemoattractant and activator of neutrophils. There is constitutive expression of IL-8 messenger ribonucleic acid (mRNA) in the lower respiratory tract of patients with CFA, and the amount of IL-8 in macrophages from patients with CFA is higher than in normal subjects [6,9,33]. In CFA, raised IL-8 mRNA levels are associated both with higher BAL neutrophil counts and greater disease severity [6].…”

“…Increased BAL neutrophil numbers are associated with extensive disease [1] and poor prognosis [2][3][4]. Neutrophil chemoattractants and activators have been shown to be present in BAL fluid of patients with CFA [5][6][7][8], and we have recently demonstrated that BAL fluid from patients with FASSc contains increased interleukin-8 (IL-8) by comparison with controls, but significantly less than CFA [9]. The neutrophil is thought to cause damage to pulmonary parenchyma through the release of proteolytic enzymes from neutrophil granules and from the generation of oxygen-derived radicals [10].…”

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony‐stimulating factor associated with the acute chest syndrome in patients with sickle cell disease

“…These findings may be explained in part by increased cytokine production, which leads to increased vascular permeability as well as increased adherence of the endothelium and red cells. IL-8 levels are elevated in the sputum and/or BALF of patients with many lung diseases, including adult respiratory distress syndrome (Lynch et al, 1992;Grunewald et al, 1993;Lipschik et al, 1993;Sekido et al, 1993;Southcott et al, 1995;Nocker et al, 1996;Bohnet et al, 1997;Takizawa et al, 1997). In vitro studies demonstrated that exposure to IL-8 increases the adherence of sickle erythrocytes to endothelium, but no in vivo role for IL-8 has been described in the context of SCD (Kumar et al, 1996).…”

Idiopathic pulmonary fibrosis biomarkers: clinical utility and a way of understanding disease pathogenesis

“…When compared directly, the IPF population had significantly greater levels of IL-8 than those with systemic rheumatologic disease. 85 A similar study of BALF samples from IPF patients attempted to correlate IL-8 levels, neutrophilia, and radiographic fibrosis with results. The authors found that IL-8 and neutrophils levels were significantly elevated in IPF compared to controls.…”