Abstract
BackgroundThere is increasing evidence pointing to the important role of tumor necrosis factor-alpha (TNF-α), a key inflammatory and apoptotic mediator in urticarial inflammation. However, the role of the TNF-α system and Fas/Fas ligand (FasL) in the apoptosis-inducing pathways in chronic spontaneous urticaria (CSU), remain unclear.AimTo determine circulating concentrations of TNF-α, soluble TNF-α receptor type 1 and type 2 (sTNF-R1 and sTNF-R2, respectively) as well as soluble Fas (sFas) and FasL (sFasL) in CSU subjects.MethodsSerum TNF-α, sTNF-R1, sTNF-R2, sFas, sFasL concentrations were measured using enzyme-linked immunosorbent assay in CSU subjects and in the healthy subjects.ResultsTNF-α concentrations were significantly higher in CSU subjects and moderate-to-severe CSU than in the controls, while there were no significant differences in TNF-α concentrations between subjects with mild CSU and the controls. sTNF-R1 and sTNF-R2 concentrations were significantly higher in all CSU and moderate-severe CSU subjects vs. the controls. Serum concentrations were also significantly higher in mild CSU vs. the controls, but not in moderate-severe CSU vs. mild CSU. No significant differences were observed in sFas and sFasL concentrations between CSU subjects and the healthy controls. Significant correlations were found between concentrations of TNF-α and its receptors, as well as sTNF-R1 and sTNF-R2, but not with the urticaria activity score (UAS). There was no relationship between TNF-α/sTNF-R1/sTNF-R2 and sFas/sFasL pathways in CSU.ConclusionsCSU is associated with the activation of the TNF-α/receptors signaling pathway, marked by increased circulating concentrations of TNF-α, sTNF-R1 and sTNF-R2, which are related to each other in this disease. In contrast, the circulating sFas/FasL system is not up-regulated in CSU, and sFas/sFasL may not be a useful marker of the activity/severity of urticarial processes. Considering the lack of significant changes in sFas/sFasL (mainly reflecting systemic apoptosis) in CSU patients, it appears that elevated serum TNF-α concentrations are related to its pro-inflammatory function rather than an enhanced systemic apoptotic response in CSU.
Highlights
Chronic spontaneous urticaria (CSU) is associated with autoimmune processes and a systemic inflammatory response [1,2,3].Tumor necrosis factor alpha (TNF-α) plays a central role in inflammatory processes, immune regulation and apoptosis
chronic spontaneous urticaria (CSU) is associated with the activation of the tumor necrosis factor alpha (TNF-α)/receptors signaling pathway, marked by increased circulating concentrations of TNF-α, Soluble tumor necrosis factor receptor type 1 (sTNF-R1) and Soluble tumor necrosis factor receptor type 2 (sTNF-R2), which are related to each other in this disease
Serum concentrations of TNF‐α and its receptors TNF-α concentrations were significantly higher in CSU subjects and moderate-to-severe CSU than in the controls [median and IQR 18.25 (17.04–19.62) and 19.01 (17.34–20.24) vs 16.89 (16.45–18.40) pg/ml; p < 0.05] (Fig. 1), while there were no significant differences in TNF-α concentrations between subjects with mild [median and IQR 17.49 (16.90–19.62) pg/ml] and moderate-to-severe CSU [median and IQR 19.01 (17.34– 20.24) pg/ml] (Fig. 1)
Summary
Tumor necrosis factor alpha (TNF-α) plays a central role in inflammatory processes, immune regulation and apoptosis. Fas ligand (FasL CD95L), a membrane molecule, belonging to the TNF family, interacts with Fas (CD95/Apo-1)—a cell surface receptor that is regulated by their soluble forms sFasL and sFas, respectively [11, 12]. The role of TNF family molecules involved in inflammation and apoptosis in CSU has not yet been fully understood [15, 16]. There is increasing evidence pointing to the important role of tumor necrosis factor-alpha (TNF-α), a key inflammatory and apoptotic mediator in urticarial inflammation. The role of the TNF-α system and Fas/ Fas ligand (FasL) in the apoptosis-inducing pathways in chronic spontaneous urticaria (CSU), remain unclear
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