Neutralization of both IL-1 α/IL-1β plays a major role in suppressing combined cigarette smoke/virus-induced pulmonary inflammation in mice

Publication date: Available online 15 March 2017 Source:Pulmonary Pharmacology & Therapeutics Author(s): Hannes Bucher, Samuel Mang, Martina Keck, Michèl Przibilla, David Lamb, Felix Schiele, Mareike Wittenbrink, Klaus Fuchs, Birgit Jung, Klaus J. Erb, Daniel Peter Smoking is an important risk factor for the development of chronic obstructive pulmonary disease (COPD) and viral infections are believed to be major triggers of exacerbations, which periodically lead to a worsening of symptoms. The pro-inflammatory IL-1 family members IL-1α and IL-1β are increased in COPD patients and might contribute to disease pathology. We investigated whether individual or combined inhibition of these cytokines reduced lung inflammation in cigarette smoke (CS)-exposed and H1N1-infected BALB/c mice. Animals were treated with individual or combined antibodies (Abs) directed against IL-1α, IL-1β or IL-1R1. Cells in BAL fluid and cytokines/chemokines in lung homogenate were determined. The viral load was investigated. Blocking IL-1α had significant suppressive effects on total cells, neutrophils, and macrophages. Furthermore, it reduced KC levels significantly. Blocking of IL-1β did not provide significant activity. In line with the in vivo findings, IL-1α Abs but not IL-1β Abs reduced levels of TNF-α and IL-6 in H1N1 infected primary human bronchial epithelial air-liquid-interface cell culture. Concomitant usage of Abs against IL-1α/IL-1β revealed strong effects i...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research