interleukin-8 and Tobacco-Use-Disorder

Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Cilomilast, a phosphodiesterase-4 inhibitor, inhibits cigarette smoke-induced neutrophilia. This study was aimed to explore whether cilomilast, in a human bronchial epithelial cell line (16-HBE), counteracted CSE effects. In particular, TLR4 expression, IP-10 and IL-8 release, lymphocyte and neutrophil chemotactic activity and ERK and IkBa phosphorylation in CSE and LPS-stimulated 16-HBE were assessed. CSE increased TLR4 expression, reduced IP-10 release and lymphocyte chemotactic activity and increased IL-8 release and neutrophil chemotactic activity. Cilomilast reduced TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. All these cilomilast mediated effects were associated with a reduced ERK1/2 and with an increased IkBa phosphorylation. In conclusion, the present study provides compelling evidences that cilomilast may be considered a possible valid therapeutic option in controlling inflammatory processes present in smokers.

Topics: Cell Line; Chemokine CXCL10; Chemotaxis; Cyclohexanecarboxylic Acids; Gene Expression Regulation; Humans; Interleukin-8; Lymphocytes; Nitriles; Phosphodiesterase 4 Inhibitors; Respiratory Mucosa; Signal Transduction; Smoke; Tobacco Use Disorder; Toll-Like Receptor 4

In this prospective longitudinal clinical study, we evaluated the role of proinflammatory cytokine IL-8 and its clinical relevance in patients with fibromyalgia (FM) who fulfilled clearly defined inclusion and exclusion criteria and underwent a 3-week inpatients multidisciplinary pain therapy.. IL-8 in sera was measured in 20 patients with FM and 80 healthy participants at 4 fixed time points: at the beginning of the study, at 10 days, 21 days, and 6 months, respectively. Pain intensity, back function, depression, nicotine/alcohol consumption, and medication were assessed in the patient group and correlated with IL-8 levels.. Before and during the inpatient therapy, the serum level of IL-8 was significantly higher in patients with FM compared with controls (P<0.001), but did not correlated with pain intensity and medication. Already at T1 there was a significant reduction of IL-8 serum level (P=0.023) in patient group. Six months after multidisciplinary pain therapy, IL-8 serum level in FM patients was still significantly higher than controls (P=0.044) but reduced approximately to normal range and correlated significantly negatively with pain intensity (r=-0.782, P=0.001). Patients with FM had significantly less pain (P<0.001) and better back function (P<0.001) at day 2 than at day 0. In addition, in patients with FM, IL-8 serum level correlated with nicotine consumption (r=0.471, P=0.042).. Our results suggest that IL-8 level contributes in patients with FM whose pain intensity and back function can be improved under influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy.

Topics: Aging; Alcohol Drinking; Back; Biomarkers; Body Mass Index; Combined Modality Therapy; Depression; Female; Fibromyalgia; Humans; Interleukin-8; Longitudinal Studies; Male; Middle Aged; Pain; Pain Measurement; Prospective Studies; Sex Characteristics; Surveys and Questionnaires; Tobacco Use Disorder; Treatment Outcome