Grażyna Chodorowska

Cytokines and anticytokines in psoriasis.

BACKGROUND Psoriasis is a chronic autoimmune hyperproliferative skin disease of varying severity affecting approximately 2-3% of the general population in the USA and Europe. Although the pathogenesis of psoriasis has not been fully elucidated, an immunologic-genetic relationship is likely. Cutaneous and systemic overexpression of various proinflammatory cytokines (TNF, interleukins, interferon-gamma) has been demonstrated in psoriatic patients. METHODS We reviewed the current database literature and summarized the involvement of cytokines and their receptors in the pathogenesis and treatment of psoriasis. RESULTS Although many cytokine/anti-cytokine therapies have been conducted, TNF antagonists in the treatment of both psoriasis arthropatica and vulgaris appear to be the most widely used clinically. Interestingly, the efficacy and tolerability of some cytokines (rhIL-11 or ABX-IL-8,) were found to be much lower than expected. CONCLUSIONS Preliminary results obtained with cytokine and anti-cytokine therapies appear promising and as such continued research is clearly indicated.

C‐reactive protein and α2‐macroglobulin plasma activity in medium–severe and severe psoriasis

Background  An acute phase of psoriasis can be induced by cytokines involved in psoriatic pathogenic phenomena. Activation of the acute phase reaction by proinflammatory cytokines (including interleukins 1 and 6, tumour necrosis factor α) may account for systemic symptoms in severe psoriasis, especially in pustular and arthropathic forms of this disease.

Lipid Disturbances in Psoriasis: An Update

Psoriasis is a common disease with the population prevalence ranging from 2% to 3%. Its prevalence in the population is affected by genetic, environmental, viral, infectious, immunological, biochemical, endocrinological, and psychological factors, as well as alcohol and drug abuse. In the recent years, psoriasis has been recognised as a systemic disease associated with numerous multiorgan abnormalities and complications. Dyslipidemia is one of comorbidities in psoriatic patients. Lipid metabolism studies in psoriasis have been started at the beginning of the 20th century and are concentrated on skin surface lipids, stratum corneum lipids and epidermal phospholipids, serum lipids, dermal low-density lipoproteins in the psoriatic skin, lipid metabolism, oxidative stress and correlations between inflammatory parameters, lipid parameters and clinical symptoms of the disease. On the basis of the literature data, psoriasis can be described as an immunometabolic disease.

Serum Levels of Selected Th17 and Th22 Cytokines in Psoriatic Patients

Introduction. Psoriasis is a T cell-mediated inflammatory disease in which pathogenesis T helper (Th) lymphocytes (Th1, Th17, and Th22) play an important role. The aim of the study was to assess the serum levels of some cytokines involved in the Th17 and Th22 responses in psoriatic patients. Material and Methods. The study comprised 60 psoriatic patients and 30 healthy controls. In the serum collected from psoriatic patients and healthy controls, the concentrations of IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 were examined with ELISA kits. Severity of psoriatic skin lesions was assessed by means of PASI, BSA, and PGA scores. Results. IL-6, IL-20, and IL-22 concentrations were significantly higher in psoriatic patients in comparison with the control group. The positive correlations between the concentrations of IL-22 and IL-20 and severity of psoriasis assessed with PASI and BSA scores as well as IL-17 and PASI score were found. There was also a positive correlation between IL-23 and IL-17 concentrations. Conclusions. Results of the conducted studies suggest that Th22 response may contribute to the skin and systemic inflammatory disease in psoriasis. It seems that early identification of soluble biomarkers and initiation of well-matched treatment may prevent exacerbation and progression of psoriasis.

Plasma concentrations of IFN-γ and TNF-α: in psoriatic patients before and after local treatment with dithranol ointment

IFN‐γ and TNF‐α plasma levels were measured before and after local treatment in 27 patients. Twenty healthy subjects served as controls. Plasma concentrations of IFN‐γ and TNF‐α were significantly higher before treatment (178.7 ± 11.9 pg/ml and 31.9 ± 11.6 pg/ml, respectively) compared to the control group (139.6 ± 7.86 pg/ml and 17.1 ± 7.7 pg/ml, respectively). After treatment IFN‐γ levels were significantly decreased (151.3 ± 8.3 pg/ml) toward the control group values and TNF‐α levels were observed even lower than in the controls (11.48 ± 6.8 pg/ml). No correlations were found between age, duration of psoriasis and plasma levels of cytokines. However, IFN‐γ levels were related, although not significantly, to disease severity (evidenced by the PASI score). The data support the important proinflammatory role of IFN‐γ and TNF‐α in the clinical manifestation of psoriasis.

Social support and adaptation to the disease in men and women with psoriasis

Social support was shown to be an important factor buffering negative effects of stress in a range of clinical populations. Little is known, however, about the role of social support in the population of patients with psoriasis although strong psychosocial stress has been implicated in this disease. The objective of this study was to evaluate the association between social support and selected indices of adaptation to life with the disease, including health-related quality of life, depressive symptoms and acceptance of life with the disease, in a sample of patients with psoriasis. Additionally, gender differences in these relationships were analyzed. One-hundred-four patients with psoriasis completed psychological tests measuring disease-related social support, health-related quality of life, depressive symptoms and acceptance of life with the disease. Psoriasis severity was assessed by Psoriasis Area and Severity Index. The patients reporting higher social support levels had significantly higher quality of life, lower depression levels, and higher acceptance of life with the disease. The strengths of these effects, however, were different in women and men. Higher social support was slightly more closely associated with better acceptance of life with the disease in men than in women. However, higher social support was more closely associated to lower depression and better quality of life in women than in men. Among different types of social support, tangible support was found to be the best predictor for the all adaptation indices. Effects of social support perceived by psoriasis patients on adaptation to the disease may be gender-related and exact pathways of these effects may depend on the type on the dimension of social support and the selected type of adaptation indicator. Tangible support seems the most important type of support contributing to better adaptation in both women and men with psoriasis.

Lipoprotein (a) in patients with psoriasis: associations with lipid profiles and disease severity

Background  Lipoprotein (a) [Lp(a)] is a genetically determined molecule whose role has been implied in cardiovascular pathology, and whose levels have been reported to be elevated in patients with psoriasis.

Biochemical markers of psoriasis as a metabolic disease

Psoriasis is a chronic immune mediated inflammatory skin disease with a population prevalence of 2-3%. In recent years, psoriasis has been recognized as a systemic disease associated with metabolic syndrome or its components such as: obesity, insulin resistance, hypertension and atherogenic dyslipidemia. Many bioactive substances have appeared to be related to metabolic syndrome. Based on current literature, we here discuss the possible role of adiponectin, leptin, ghrelin, resistin, inflammatory cytokines, plasminogen activator inhibitor 1, uric acid, C-reactive protein and lipid abnormalities in psoriasis and in metabolic syndrome.

Genes and structure of selected cytokines involved in pathogenesis of psoriasis.

Psoriasis is a common skin disease involving 1-4% of human population worldwide, of strong genetic background. The following cytokines are directly involved in psoriasis: TNF, IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-18, IL-19, IL-20, IL-23 whereas IL-4, IL-10, IL-12 as well as IL-11, IL-17 and IFN-gamma are rather indirectly engaged. This work is a review of some genetic factors and structure of selected cytokines and receptors and their genes location.

Rational for statin use in psoriatic patients.

Psoriasis represents a common skin disease which is clinically manifested by chronic cutaneous lesions. It has been observed that psoriasis is associated with an increased risk of cardiovascular diseases, which is contributed to the inappropriate lipid metabolism. Statins are commonly used in clinical practice to lower cholesterol concentration and, accordingly, decrease the individual risk of developing a cardiovascular episode. There have been reports that statin administration could also result in better management of psoriasis. The observed beneficial effects are contributed to the effects on lipid metabolism, including that in skin, as well as anti-inflammatory and immunomodulatory properties of statins. Simvastatin and atorvastatin were found to improve the clinical outcome in patients with psoriatic skin lesions. Clinically, the effectiveness of this novel treatment was confirmed by the significant reduction in PASI score. To date several cases have been reported in which atorvastatin or pravastatin worsened psoriasis. Based on these results, it seems that statins represent a promising class of medications which could be extensively used in psoriasis.