IL-17-producing T lymphocytes in lung tissue and in the bronchoalveolar space after exposure to endotoxin from Escherichia coli in vivo – effects of anti-inflammatory pharmacotherapy

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A systemic dose of a calcineurin-phosphatase inhibitor exerts a less complete and more selective effect on the endotoxin-induced increase in extracellular IL-17 protein and on neutrophils in BAL samples. In vitro, endotoxin also increases extracellular IL-17 protein in a co-culture of CD3-positive spleen cells and adherent mononuclear BAL cells; an increase that was inhibited by a glucocorticoid as well as by a calcineurin-phosphatase Accepted Manuscript Short title. Pharmacology of IL-17-producing T lymphocytes in lungs

Interleukin-17 cytokine signalling in patients with asthma

“…Moreover, when patients with all three degrees of disease severity were subsequently treated with a moderate daily dose of an inhaled glucocorticoid, this treatment reduced the concentration of IL-17A protein. This suggests that the net release of IL-17A protein in the airways of patients with asthma is actually sensitive to glucocorticoids under these conditions, contrasting with previously published data indicating a very low sensitivity to glucocorticoids in animal models [35,37]. However, and this may be important, the utilised glucocorticoid treatment did not markedly affect the relative number of neutrophils in induced sputum from the patients in this study.…”

“…However, when comparing the hyperresponsive subgroup of patients with a healthy control group without hyperresponsiveness, the average difference in sputum IL-17A emerged as modest, even though it was statistically significant. It cannot be ruled out that the inconsistent treatment with inhaled glucocorticoids among the patients with asthma contributed to this somewhat vague outcome, given what is known about the sensitivity of the production of IL-17A to glucocorticoids from animal and cell models [35]. Along these lines, in the study by BARZYCK et al [34] the patients with asthma did not have an increase in sputum neutrophils.…”

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

“…Even though the current findings in humans cannot be predicted from previous studies on mouse models in vivo, they are fully compatible with these studies [4,5,18,19]. They are also compatible with previous studies on the impact of organic dust on healthy volunteers [20,21].…”

“…in the lung tissue, cannot be ruled out in the production and release of the IL-17 that was detected in the current study [18,19]. Nor can an additional involvement of cell types other than T-cells be ruled out in the production and release of the IL-17 that was found in the BAL samples [19].…”

Interleukin-17 enhances the removal of respiratory syncytial virus in mice by promoting neutrophil migration and reducing interferon-gamma expression

“…Some studies have reported that IL-17 plays an important role in the immune process in host lungs, by recruitment of neutrophils to the local infection site and production of cytokines inducing neutrophil migration by stimulating the cells. This resulted in the effective removal of pathogens from the host (Laan et al, 2002;Dragon et al, 2008;Prause et al, 2009). Ryzhakov et al (2011) reported that the body produces a large number of IL-17 after infection by a virus, and that IL-17 synergistically increases the specificity of inflammation via antiviral signaling pathways.…”