Prothrombotic State in Asthma Is Related to Increased Levels of Inflammatory Cytokines, IL-6 and TNFα, in Peripheral Blood

Abstract

Recently, we have reported that asthma is associated with enhanced plasma thrombin formation and impaired fibrinolysis. The mechanisms underlying the prothrombotic state in this disease are unknown. Our aim was to investigate whether prothrombotic alterations in asthmatics are associated with inflammation. We studied 164 adult, white, stable asthmatics and 72 controls matched for age, sex, body mass index (BMI), and smoking. Plasma tumor necrosis factor α (TNFα), interleukin (IL)-6, and serum periostin were evaluated using ELISAs, and their associations with thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were later analyzed. Asthma was characterized by 62% higher plasma IL-6 and 35% higher TNFα (both, p < 0.0001). Inflammatory cytokines were higher in sporadic and persistent asthmatics compared to controls, also after adjustment for potential confounders. IL-6 was inversely related to the forced expiratory volume in 1 s/vital capacity (FEV1/VC) spirometry index after correction for age, sex, and BMI. IL-6 and TNFα were associated with C-reactive protein in asthmatics (β = 0.6 [95% CI, 0.54–0.67] and β = 0.33 [95% CI, 0.25–0.41], respectively) and controls (β = 0.43 [95% CI, 0.29–0.57] and β = 0.33 [95% CI, 0.18–0.48], respectively). In asthma, IL-6 and TNFα positively correlated with the endogenous thrombin potential (β = 0.35 [95% CI, 0.28–0.42] and β = 0.15 [95% CI, 0.07–0.23], respectively) but not with CLT or platelet markers. However, TNFα predicted CLT in a multiple linear regression model. Periostin was not associated with any hemostatic parameters. Enhanced thrombin generation is driven in asthma by a systemic inflammatory state mediated by IL-6 and to a lesser extent TNFα, however, not periostin. TNFα might contribute to impaired fibrinolysis.