Interleukin-8 (IL-8): The Major Neutrophil Chemotactic Factor in the Lung

Abstract

A number of novel chemotactic cytokines are becoming increasingly recognized as important participants in the elicitation of specific inflammatory cells from the peripheral blood to sites of inflammation. Recent observations have now demonstrated that certain chemotactic cytokines possess specificity for the selected movement of individual immune/inflammatory cell populations. One of the more studied chemotactic cytokines is a neutrophil chemotactic factor identified as interleukin-8 (IL-8). This polypeptide mediator is produced in abundance by mononuclear phagocytic cells, as well as a number of non-inflammatory cells. This latter list includes both fibroblasts and epithelial cells. Moreover, the synthesis of IL-8 by fibroblasts and epithelial cells involves stimulus specificity, as the production of this mediator by non-inflammatory cells is dependent upon an initial host response. In the context of the lung, the alveolar macrophage appears to play a central role by generating factors, such as interleukin-1 and tumor-necrosis factor, which are potent stimuli for the induction of IL-8 by the lung fibroblasts and type II epithelial cells. The cascade-like interaction may lead to the rapid production of significant quantities of IL-8 by the lung and may selectively recruit neutrophils to the pulmonary interstitium and/or airspace. This sequence of events, which leads to cytokine networking in the lung, may be an important phenomenon for the generation of a major chemotaxin important to a variety of lung diseases.

In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on <i>COX-2</i> and <i>IL-8</i> gene expression

“…IL-8 is a potent neutrophil chemotactic factor in the lung and its expression by various cells plays a crucial role in neutrophil recruitment leading to lung inflammation (Kunkel et al, 1991). COX-2 is the inducible form of the cyclooxygenase enzyme, regulated by cytokines and mitogens, and is responsible for prostaglandin synthesis associated with inflammation (FitzGerald, 2003).…”

“…IL-8 and COX-2 are both linked to inflammation and oxidative stress (Kunkel et al, 1991;Uchida, 2008). IL-8 is a potent neutrophil chemotactic factor in the lung and its expression by various cells plays a crucial role in neutrophil recruitment leading to lung inflammation (Kunkel et al, 1991).…”

“…An in vitro study that followed supported the potential for isoprene SOA to affect the levels of oxidative stress genes . In this study we chose to examine the gene expression levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2), not only for their links to inflammation and oxidative stress (Kunkel et al, 1991;Uchida, 2008) but also because both have been examined in previous studies using the EAVES for fresh and aged diesel exhaust (Lichtveld et al, 2012). Other studies on air pollution mixtures have also examined IL-8 as a biological endpoint due to its involvement with inflammation (Zavala et al, 2014;Ebersviller et al, 2012a, b;Doyle et al, 2004Doyle et al, , 2007.…”

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

“…The main chemotactic factor for neutrophils in the blood and bronchoalveolar lavage (BAL) fluids of patients with ARDS has been shown to be the cytokine interleukin (IL)-8, and other products of inflammation make a lesser contribution [6]. Higher levels of IL-8 are present in BAL samples from nonsurvivors than survivors with ARDS [7], and elevations of IL-8 concentration in BAL fluid predict progression to ARDS in at-risk populations [8].…”

Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation

“…Based on the results of the present in vitro observations, it is therefore possible that the observed decrease in levels of free IL-8 may be attributed to the enhanced inhibitory effect of glucocorticoids on T-cells. Although PBMC may produce significant amounts of this chemokine, a direct inhibitory effect on other cells capable of producing IL-8, such as epithelial cells, fibroblasts and mast cells, cannot be excluded [33]. Further studies on the in vitro effects of MTX on the production of IL-8 and other mediators by these cells are required.…”