The relationship between circulating concentrations of interleukin 17 and C reactive protein in chronic spontaneous urticaria

Abstract Background Up-regulation of interleukin 17 (IL-17) family cytokines and acute phase response have been observed in patients with chronic spontaneous urticaria (CSU). It has been demonstrated that IL-17 stimulates C-reactive protein (CRP) expression. Aim To determine relationship between circulating concentrations of IL-17 and CRP in CSU. Methods Concentrations of IL-17 in plasma and CRP in serum were measured in patients with CSU of varying severity and in the healthy subjects. Results IL-17 and CRP concentrations were significantly higher in CSU patients as compared to the healthy subjects. In addition, there were significant differences in IL-17 and CRP concentrations between CSU patients with mild, moderate-severe symptoms and the healthy subjects. CRP did not correlate significantly with IL-17. Conclusions Increased circulating IL-17 concentration may represent an independent index of systemic inflammatory response in CSU, which is not related to increased CRP concentration

Interplay between acute phase response and coagulation/fibrinolysis in chronic spontaneous urticaria

Abstract Background Chronic spontaneous urticaria (CSU) is associated with activation of systemic inflammatory response and coagulation/fibrinolysis. Aim To study whether there is a relationship between the acute phase response and coagulation/fibrinolysis in chronic spontaneous urticaria (CSU) patients. Methods Serum concentrations of C-reactive protein (CRP) and interleukin 6 (IL-6), key markers of acute phase response and of D-dimer, a marker of fibrin turnover were investigated in 58 CSU patients assessed with the urticaria activity score (UAS) and the controls. Results Serum concentrations of IL-6, CRP, and D-dimer were significantly higher in CSU patients as compared with the controls. We found statistically significant correlations between D-dimers concentrations and the inflammatory markers: CRP and IL-6 as well as UAS. Conclusions Markers of inflammation (IL-6 and CRP) and of fibrinolysis (D-dimer) are related to each other in CSU, suggesting a possible cross-talk between inflammation and coagulation/fibrinolysis. It might be implicated in pathogenesis of the disease and may be associated with higher risks of cardiovascular diseases in CSU patients

Tumor necrosis factor-alpha and Fas/Fas ligand signaling pathways in chronic spontaneous urticaria

Abstract Background 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. 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. Aim To 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. Methods Serum TNF-α, sTNF-R1, sTNF-R2, sFas, sFasL concentrations were measured using enzyme-linked immunosorbent assay in CSU subjects and in the healthy subjects. Results TNF-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. Conclusions CSU 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

Prolactin and the skin: A dermatological perspective on an ancient pleiotropic peptide hormone

The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator of lactation and reproduction. However, based on the almost ubiquitous distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary PRL-expressing tissues, a vast range of PRL actions “beyond the mammary horizon” has now been documented or claimed. For example, PRL modulates hair growth in domestic animals with seasonal hair growth changes (“PRL–pelage axis”). Given that the mammary gland is an epidermal derivative, it is not surprising that the pilosebaceous unit, another epidermal derivative, has also surfaced as a prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact that murine and human hair follicles even synthesize PRL strongly invites one to explore fully the dermatological dimensions of this multifunctional, cytokine-like neuroendocrine bioregulator, which remain insufficiently charted. After describing the relevant essentials of general PRL/PRLR biology, we summarize clinical observations that provide insights into how PRL may impact on the skin, and define important research frontiers and controversies in the quest to better characterize the complex role of PRL in human skin biology and pathology. Focusing on psoriasis, alopecia, and stress-related dermatoses, we then discuss the possible role of PRL/PRLR in cutaneous pathology, and identify potential therapeutic targets for the management of these skin disorders. We close by delineating major open questions at this emerging frontier of basic and clinical cutaneous neuroendocrinology, and argue that systematic exploration of the “PRL–skin connection” will fertilize the development of previously unreported neuroendocrinological strategies for managing selected skin disorders