Abstract
The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE mice; in which a systemic TNF-α overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however depend on the duration of CS exposure.
Highlights
Aberrant cytokine profiles have been linked to several immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD) [1,2,3]
WT mice exposed to cigarette smoking (CS) for 2 weeks showed a modest, but significant increase in the absolute numbers of neutrophils, dendritic cells (DC) and CD4+ T-lymphocytes compared to air-exposed control mice (Fig 1C–1E)
In the lungs of TNFΔARE mice exposed to 4 weeks of air, which is at the age of 10 weeks, we denoted an increase in neutrophils, dendritic cells, CD4+ and CD8+ T cells
Summary
Aberrant cytokine profiles have been linked to several immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD) [1,2,3]. TNF-α, a prominent pro-inflammatory cytokine, appears to be an important
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