Neutrophilic Alveolitis in Idiopathic Pulmonary Fibrosis: The Role of Interleukin-8

Abstract

Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine in the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis

“…To support our hypothesis, we studied the content of neutrophil-related cytokines and neutrophil products in BALF and serum or plasma of this patient. IL-8 is known to have a potent neutrophil chemotactic activity [10], and to play an important role in the accumulation of neutrophils in the lungs in the adult respiratory distress syndrome (ARDS) [11], idiopathic pulmonary fibrosis (IPF) [12] and diffuse panbronchiolitis (DPB) [13,14]. The concentrations of IL-8 in BALF (815 pg·mL -1 ) and serum (79.7 pg·mL -1 ) were higher in our patient compared with those of five of the seven healthy volunteers (BALF 21± 46 pg·mL -1 ; serum 2.5±5.6 pg·mL -1 ) (table 1).…”

Lazaroid U-74389F attenuates phorbol ester-induced lung injury in rabbits

“…IL-8 expression is induced in vitro in a variety of cells, including endothelial cells, alveolar epithelial cells, alveolar macrophages and pulmonary fibroblasts, in response to stimulation with proinflammatory cytokines (interleukin-1 and tumour necrosis factor-α) and to lipopolysaccharide [25][26][27][28]. Over the last few years, it has become increasingly evident that IL-8 plays an important role in the alveolar recruitment of neutrophils in the course of acute inflammatory lung disorders [12][13][14][15]. Because it has been reported that hyperoxia-stimulated, monocytederived IL-8 expression is suppressed in vitro by U-74389F [11], we looked for evidence of in vivo IL-8 release in response to PMA challenge and for a possible modulation of its production by U-74389F pretreatment.…”

“…Also, it has been reported that lazaroids are capable of suppressing the expression of the neutrophil chemoattractant cytokine interleukin-8 (IL-8) in hyperoxiastimulated monocytes cultured in vitro [11]. The latter finding may be therapeutically relevant because IL-8 has been implicated in the pathogenesis of a number of neutrophil-mediated lung disorders, including idiopathic pulmonary fibrosis [12,13], and the adult respiratory distress syndrome (ARDS) [14,15].…”

Sustained High Levels of Circulatory Interleukin-8 are Associated with a Poor Outcome in Patients with Adult Respiratory Distress Syndrome.

“…Therefore IL-8 has been implicated in a wide variety of pathological conditions characterized by neutrophil infiltration. Several authors have demonstrated increased levels of IL-8 in blood and airspaces in patients with ARDS(9-13), sepsis (18) and fibrosing alveolitis (19). On the other hand, neutrophil elastase, a powerful protease released by neutrophils , destroys the extracellular matrix, modifies airway epithelial cells, and interferes with respiratory host systems.…”