Characteristics of Proinflammatory Cytokines and Chemokines in Airways of Asthmatics: Relationships with Disease Severity and Infiltration of Inflammatory Cells.

BACKGROUND: Increased proinflammatory cytokines and chemokines might contribute to infiltration of inflammatory cells and remodeling in airways of asthma. Although these molecules may be associated with asthma, there is lack of systemic evidence showing which and how important these events are in the disease. We aimed to analyze the concentrations of these molecules in the airways and relationships with disease severity and with airway infiltration of inflammatory cells in a large cohort of asthmatics (n = 70, including 37 mild and 33 moderate/severe asthmatics) compared with controls (n = 30).

METHODS: Meso scale discovery system and commercial ELISA kits were used to measure the concentrations of proinflammatory cytokines interleukin (IL)-1β; tumor necrosis factor-alpha (TNF-α); IL-6; and IL-17 and CC and CXC chemokines CCL2, CCL4, CCL11, CCL13, CCL17, CCL22, and CCL26 and CXCL8, CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid of asthmatics and controls.

RESULTS: The concentrations of IL-1, TNF-α, IL-6, CXCL8 and CXCL10, and CCL4, CCL11, CCL17, and CCL22 were significantly elevated in asthmatics compared with controls (P < 0.05). The concentrations of TNF-α and CXCL8, but not others, were negatively correlated with severity of disease (lung function forced expiratory volume in 1 s) (TNF-α vs. total: r = -0.359, P= 0.002 vs. moderate/severe: r= -0.541, P= 0.001; CXCL8 vs. total: r = -0.327, P= 0.006 vs. moderate/severe: r = -0.625, P= 0.0001, respectively). In addition, concentrations of these two molecules were also correlated with the absolute numbers of infiltrating eosinophils and neutrophils in asthmatic airways.

CONCLUSIONS: Increased concentrations of TNF-α and CXCL8 are associated with pathogenesis of asthma. Targeting these molecules might provide an alternative therapeutic for this disease.