IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger

S Ferretti, O Bonneau, GR Dubois… - The Journal of …, 2003 - journals.aai.org
S Ferretti, O Bonneau, GR Dubois, CE Jones, A Trifilieff
The Journal of Immunology, 2003journals.aai.org
IL-17 is a cytokine implicated in the regulation of inflammation. We investigated the role of
this cytokine in neutrophil recruitment using a model of LPS-induced lung inflammation in
mice. In the bronchoalveolar lavage, LPS induced a first influx of neutrophils peaking at day
1, followed by a second wave, peaking at day 2. IL-17 levels were increased during the late
phase neutrophilia (day 2), and this was concomitant with an increased number of T cells
and macrophages, together with an increase of KC and macrophage-inflammatory protein-2 …
Abstract
IL-17 is a cytokine implicated in the regulation of inflammation. We investigated the role of this cytokine in neutrophil recruitment using a model of LPS-induced lung inflammation in mice. In the bronchoalveolar lavage, LPS induced a first influx of neutrophils peaking at day 1, followed by a second wave, peaking at day 2. IL-17 levels were increased during the late phase neutrophilia (day 2), and this was concomitant with an increased number of T cells and macrophages, together with an increase of KC and macrophage-inflammatory protein-2 levels in the lung tissue. Intranasal treatment with a neutralizing murine anti-IL-17 Ab inhibited the late phase neutrophilia. In the bronchoalveolar lavage cells, IL-17 mRNA was detected at days 1, 2, and 3 postchallenge, with a strong expression at day 2. This expression was associated with CD4+ and CD8+ cells, but also with neutrophils. When challenged with LPS, despite the absence of T cells, SCID mice also developed a neutrophilic response associated with IL-17 production. In BALB/c mice, IL-15 mRNA, associated mainly with neutrophils, was evidenced 1 day after LPS challenge. In vitro, IL-15 was able to induce IL-17 release from purified spleen CD4+ cells, but not spleen CD8+ or airway neutrophils. We have shown that IL-17, produced mainly by CD4+ cells, but also by neutrophils, plays a role in the mobilization of lung neutrophils following bacterial challenge. In addition, our results suggest that IL-15 could represent a physiological trigger that leads to IL-17 production following bacterial infection.
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