*Emilia Tekely1, Beata Szostakiewicz-Grabek2, Dorota Krasowska3, Grażyna Chodorowska3
Serum levels of chemerin and pigment epithelium-derived factor in patients with psoriasis
Ocena stężeń chemeryny i czynnika wzrostu pochodzącego z nabłonka barwnikowego w surowicy krwi u chorych na łuszczycę
12nd Department of Anesthesiology and Intensive Care, Medical University of Lublin
Head of Department: Mirosław Czuczwar, MD, PhD
2Dermatology Outpatient Clinic, Stefan Wyszyński Province Specialist Hospital in Lublin
Head of Department: Adam Umer, MD
3Chair and Department of Dermatology, Venerology and Pediatric Dermatology, Medical University of Lublin
Head of Department: Professor Dorota Krasowska, MD, PhD
Wstęp. Łuszczyca jest wieloczynnikową, przewlekłą chorobą zapalną powiązaną z wieloma współistniejącymi zaburzeniami ogólnoustrojowymi. Tkanka tłuszczowa oprócz tego, że stanowi źródło energii dla organizmu ludzkiego, spełnia także rolę aktywnego narządu wewnątrzwydzielniczego, wydzielając/uwalniając adipokiny. Adipokiny odgrywają istotną rolę w metabolizmie lipidów, modulują procesy zapalne, hemostazę, uczestnicząc w patogenezie wielu chorób zapalnych. Rola adipokin w patogenezie łuszczycy wciąż nie jest w pełni poznana.
Cel pracy. Celem pracy była ocena stężeń wybranych adipokin w surowicy krwi pacjentów z łuszczycą pospolitą oraz badanie możliwych zależności z wybranymi parametrami laboratoryjnymi i klinicznymi.
Materiał i metody. W surowicy krwi 66 pacjentów i 40 osób zdrowych oznaczono stężenia chemeryny i PEDF, stosując metodę immunoenzymatyczną ELISA. Otrzymane wyniki badano pod kątem istnienia zależności pomiędzy stężeniami wybranych adipokin a nasileniem klinicznym łuszczycy (PASI), zaburzeniami masy ciała (BMI) i parametrami stanu zapalnego: CRP, SR.
Wyniki. W grupie pacjentów z łuszczycą stwierdzono istotnie wyższe stężenia chemeryny i PEDF niż u zdrowych osób. W grupie pacjentów z łuszczycą stwierdzono istotne statystycznie korelacje pomiędzy stężeniem chemeryny a parametrami stanu zapalnego (CRP, SR) oraz składowymi profilu lipidowego. Stwierdzono istotną statystycznie zależność pomiędzy surowiczym stężeniem PEDF a wartością wskaźnika BMI w grupie chorych na łuszczycę z nadwagą.
Wnioski. Wyniki przeprowadzonych badań wskazują na możliwy udział badanych adipokin w procesach patofizjologicznych prowadzących do rozwoju łuszczycy.
Introduction. Psoriasis is a multifactorial chronic inflammatory disease associated with multiple comorbidities (obesity, cardiovascular diseases, metabolic syndrome). Adipose tissue is not only an energy-storing organ but also a major source of adipokines. Affecting vascular function, adipocyte metabolism and immune regulation, adipokines are participants in the pathogenesis of various diseases. The association of the novel adipokines with psoriasis is still obscure.
Aim. The aim of this study was to investigate serum levels of adipokines in patients with chronic plaque psoriasis.
Material and methods. Serum fasting chemerin and pigment epithelium-derived factor (PEDF) levels were examined by enzyme-linked immunosorbent assay (ELISA) in 66 patients with psoriasis and 40 healthy controls. Possible correlations were searched between the serum adipokines concentrations and the Psoriasis Area and Severity Index (PASI), Body Mass Index (BMI) and inflammatory marker: C-reactive protein (CRP), erythrocyte sedimentation rate (SR).
Results. Patients with psoriasis showed considerably higher serum levels of chemerin and PEDF than healthy controls. There were no correlations between the above measures and PASI. Serum chemerin levels in psoriatic patients were significantly correlated with inflammatory markers and abnormalities of lipid profile. PEDF levels were significantly positively correlated with BMI in the overweight psoriatic patients.
Conclusions. In summary, the results of the conducted study indicate that the examined adipokines can be involved in the pathophysiology of psoriatic inflammation.
Psoriasis is a chronic immune-mediated inflammatory skin disease affecting more than 2% of the world population (1, 2). The pathogenesis of psoriasis is complex and it has genetic, autoimmune and hormonal background (3). A number of recent studies have revealed an association between psoriasis and systemic disorders leading to the development of concomitant immune-mediated inflammatory diseases (3-5). It has been noted that systemic chronic inflammation associated with increased interaction of inflammatory mediators of various origin, including cytokines, growth factors, platelet-derived factors, adipokines, abnormal lipid profile and the activation of vascular endothelium, may be a common pathophysiological basis for psoriasis and other immune-mediated inflammatory diseases (6, 7). It appears, that the metabolic syndrome and its components, in particular, can constitute a link between cardiovascular diseases and type 2 diabetes mellitus in psoriatic patients (4, 5, 8). Understanding the importance of white adipose tissue as an endocrinologically and immunologically active organ has shed new light on the pathophysiological processes of psoriasis, especially on the possible role of bioactive mediators produced by the adipose tissue cells, namely adipokines (6, 9). Recent data indicate that adipokines are involved in the homeostasis maintenance through regulating bodily functions, such as: glucose and lipid metabolism, blood pressure, tissue sensitivity to insulin as well as immune-mediated and inflammatory processes (6, 9-11). Epidemiological surveys reveal the association of psoriasis with obesity, glucose intolerance/diabetes mellitus, hypertension and cardiovascular diseases.
Chemerin is a recently discovered 18 kDa primarily inactive protein that regulates adipocyte differentiation and stimulates chemotaxis and activation of dendritic cells and macrophages (11, 12). This adipokine has low biological activity and requires further extracellular C-terminal processing (11, 13, 14). More recent studies have shown that chemerin is elevated in tissues and fluids in inflammatory conditions and serum chemerin levels correlate with levels of the proinflammatory cytokines such as: tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and also with CRP (13, 14). In the dermis of early psoriasis leasions Albanesi et al. reported high expression of chemerin together with increased number of plasmacytoid dendritic cells (pDCs) however in the chronic plaques low chemerin expression and pDCs were found (15, 16). Nakajima et al. described elevated chemerin levels in the serum of psoriatic patients (16). Recently chemerin was reported as an adipokine regulating adipogenesis and adipocyte metabolism (11, 14, 17). In another study serum level of chemerin was highly correlated with several markers of inflammation and components of the metabolic syndrome (12). Chemerin has also been detected on dermal endothelial vessels of systemic lupus erythematosus (SLE) (15, 18). The dual role of this adipokine may be a link between chronic inflammation and obesity related disorders.
PEDF is a multifunctional glycoprotein that belongs to the superfamily of serine protease inhibitors with potent antiangiogenic and neurotrophic properties (19-21). It was first purified from the conditioned medium of human retinal pigment epithelial cells but a recent study showed that PEDF is widely distributed in variety of human tissues, including adipocytes, vascular, inflammatory cells and skin (20, 22). Recently published studies found that serum levels of PEDF are strongly associated with components of metabolic syndrome (19, 20, 22). Chen et al. recently reported that increased serum level of PEDF independently predicted the development of the metabolic syndrome in a 10 year prospective study (23). Serum PEDF correlated with several factors closely related to insulin resistance, BMI, triglycerides, systolic blood pressure. Two other studies describe a significant correlation between serum level of PEDF and obesity in humans indicating adipose tissue as the main source of PEDF (19, 21, 24). Rychli et al. suggested that PEDF can have a protective role in atherosclerosis because of its anti-oxidant, anti-inflammatory and anti-thrombotic properties in the vessel wall (25). Nakajima et al. examined PEDF levels in the serum of patients with psoriasis compered to healthy controls (22). Circulating PEDF levels were significantly higher in psoriatic patients than in control subjects. Their findings might suggest that PEDF could mediate anti-inflammatory actions in psoriasis.
Taking into consideration, that the results of previous studies are often inconclusive, the own study has been undertaken to evaluate the selected adipokines in the psoriatic patients and to investigate the potential role of adipokines in systemic abnormalities as part of the metabolic syndrome. In particular, the present study focuses on:
1. The assessment of the serum levels of selected adipokines – chemerin and PEDF in patients suffering from psoriasis as compared with healthy controls.
2. The assessment of the possible relationship between the disease severity and the serum levels of selected adipokines in patients with psoriasis.
3. The assessment of the possible correlations between the serum levels of selected adipokines and selected laboratory indicators of inflammation, lipid profile and the components of the metabolic syndrome.
Material and methods
The study was carried out on 66 adult male patients diagnosed with the plaque-type psoriasis and treated at the Department of Dermatology, Venereology and Paediatric Dermatology of the Medical University of Lublin. The control group consisted of 40 healthy volunteers whose sex and age matched the study group. The complete medical histories of patients with psoriasis were reviewed, their general health condition was assessed. The used protocol was approved by the Committee on Ethics of the Medical University of Lublin and all the psoriatic patients gave informed consent to participate in the study.
Psoriasis severity was evaluated by the PASI score. The PASI score below 10 defined psoriasis as mild, a score >10 was considered as moderate to severe. The weight and height of all patients and volunteers from the control group were measured.
BMI was calculated as the weight in kilograms divided by square of height in metres and participants were classified as being of normal weight (≥ 18.5 and < 25), overweight (≥ 25 and < 30), or obese (≥ 30).
Venous blood samples were collected from both psoriatic patients and healthy individuals. The laboratory tests included: lipid profile parameters (total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides), CRP concentration and SR. The serum concentrations of chemerin and PEDF were measured by enzyme-linked immunosorbent assay (ELISA) using commercially available kits according to the manufacturer’s instructions (Biovendor Human Chemerin ELISA; Biovendor GmbH Heidelberg, Germany, PEDF ELISA Kit; Wuhan EIAAB Science CO Wuhan, China).
Statistical analyses were performed using Statistica ver. 10.0 PL. Results are presented as mean, standard deviation (SD) or median with interquartile as appropriate. The statistical comparison among groups was calculated by the Mann-Whitney test. The correlation analysis was performed by calculating the Spearman coefficient correlation. A p value < 0.05 was considered as statistically significant.
In our study no statistically significant differences were found between patients and controls (p > 0.05) regarding age, sex. The mean PASI was 21.09 (tab. 1).
Tab. 1. Assessment of psoriasis severity using the PASI score
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