Anna Michalak-Stoma

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.

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.

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.

The effect of Propionibacterium acnes on maturation of dendritic cells derived from acne patients' peripherial blood mononuclear cells.

Propionibacterium acnes (P. acnes) has been implicated in the pathogenesis of acne vulgaris which is the most common cutaneous disorder. It has a proinflammatory activity and takes part in immune reactions modulating the Th1/Th2 cellular response. The exposure of dendritic cells (DCs) to whole bacteria, their components, cytokines or other inflammatory stimuli and infectious agents induces differentiation from immature DCs into antigen-presenting mature DCs. The aim of the study was to evaluate the capability of P. acnes to induce the maturation of DCs. We stimulated monocyte derived dendritic cells (Mo-DCs) from acne patients with various concetrations of heat-killed P. acnes (10(6)-10(8) bacteria/ml) cultured from acne lesions. The results showed an increase in CD80+/CD86+/DR+ and CD83+/CD1a+/DR+ cells percentage depending on the concetration of P. acnes. The expression of CD83 and CD80 (shown as the mean fluorescence intensity - MFI) increased with higher concetrations of P. acnes. There were also significant correlations between MFI of CD83, CD80, CD86 and concetration of P. acnes. The study showed that P. acnes in the concetration of 10(8) bacteria/ml is most effective in the induction of Mo-DCs maturation. Futher studies concerning the influence on the function of T cells are needed.

Plasma Interleukin-18 and Dendritic Cells in Males with Psoriasis Vulgaris

Peripheral blood dendritic cells seem to play a crucial role in psoriatic inflammatory processes. The aim of our study is to investigate the relationship between plasma interleukin-18 (IL-18) levels and blood dendritic cells in psoriatic patients. IL-18 plasma levels were measured by ELISA. Phenotypes of dendritic cell subsets were analyzed by double-colour flow cytometry. Plasma IL-18 level in psoriatic males was significantly higher, whereas counts of BDCA-2+ cells were lower than in the control group. The myeloid/plasmacytoid ratio was significantly higher in the patient group compared to the control one. In the patient group, significant negative correlations between plasma IL-18 level and both the BDCA-1+ and BDCA-2+ counts were found. BDCA-1+ counts correlated negatively with percentage of skin involvement. IL-18 seems to play a role in psoriasis pathogenesis. The decreased counts of blood plasmacytoid DCs in psoriatic patients might result from IL-18 down-regulation of plasmacytoid DC precursor proliferation.

Videocapillaroscopic Alterations in Alopecia Areata

Alopecia areata (AA) is a common hair disorder observed in dermatological practice; however, the exact mechanisms that lead to the hair loss are still unknown. Disturbances in the blood supply of hair follicles may be one of the elements in the complex pathogenesis of AA. Nailfold videocapillaroscopy is a noninvasive technique that allows analysis of skin microcirculation in vivo. The aim of the study was the videocapillaroscopic assessment of skin microcirculation in AA patients. The study included 44 patients with patchy alopecia areata, 27 with alopecia universalis or totalis, and 40 healthy volunteers. Nailfold videocapillaroscopy was performed in all participants according to a standard protocol. Obtained images were assessed qualitatively and quantitatively. Two types of videocapillaroscopic images were distinguished in the study. Abnormal videocapillaroscopic images were found in 42% of patients. Tortuous and branching capillaries (P = 0.013, P = 0.001), decreased density of capillaries (P = 0.009), enlargement of the efferent limb (P < 0.017), or top part of the loop (P = 0.009) were observed significantly more often than in the control group. Only some patients with AA presented with microvascular abnormalities characterised by altered videocapillaroscopic images. More studies, including larger group of patients with AA, are required to determine the role of observed videocapillaroscopic alterations in AA.

Suppressed Programmed Death 1 Expression on CD4

Psoriasis is a chronic inflammatory disease mediated by T cell immunity. Programmed death 1 (PD-1), a coinhibitory receptor, plays an important role in immune regulation and maintaining peripheral tolerance. The aim of the study was to compare the expression of PD-1 on the peripheral T cells between psoriatic patients and healthy controls. The study included 75 psoriatic patients and 52 healthy volunteers. The percentages and absolute numbers of CD3+, CD4+, CD8+, CD4+PD-1+, and CD8+PD-1+ T cells were analyzed using flow cytometry. The absolute numbers and percentages of CD4+PD-1+ and CD8+PD-1+ T cells were significantly decreased in the psoriatic patients in comparison with the control group. No significant correlations were found between the absolute numbers and percentages of CD4+PD-1+ or CD8+PD-1+ T cells and clinical characteristics of psoriasis. Decreased PD-1 expression on the T cells may be responsible for impaired negative regulation of immune response in psoriasis pathogenesis.

Eruption of palmoplantar pustular psoriasis in patient treated with anti-androgen therapy for prostate cancer and aggravation of lesions after statin treatment

The article focuses on the eruption of palmoplantar pustular psoriasis, which was documented in a 53-year-old man diagnosed with prostate cancer with bone metastases. This clinical finding was made during routine hormone therapy and palliative radiotherapy. The local improvement in skin lesions was achieved following administration of topical ointments and the use of UVA 311 nm radiation therapy. The management of prostate cancer in this subject resulted in malaise, onset of diabetes mellitus and increased concentration of serum lipids. Interestingly, a few days after the statin treatment was initiated, the intensive pustule eruption was observed as well as severe pain and burning sensation in the palms and soles. The dermatological treatment led to significant improvement. The patient is still receiving oncological therapy and is monitored by dermatologists on a regular basis.

Decreased blood CD4+PD-1+ and CD8+PD-1+ T cells in psoriatic patients with and without arthritis

Introduction Psoriasis with and without arthritis have common immunological mechanisms which among others involve the interactions between cytokines produced by T cells, including Th1, Th17 and Th22. Although quite a lot is known about psoriasis pathogenesis, the cause of chronic immune activation and response in the disease remains unclear. One of the negative regulators of the immune system is programmed death 1 (PD-1). Aim To assess the expression level of PD-1 in the peripheral T cells of psoriatic patients with and without arthritis. Material and methods The study included 23 psoriatic patients with arthritis, 52 psoriatic patients without arthritis and 52 healthy controls. The percentages of CD3+, CD4+, CD8+, CD4+PD-1+ and CD8+PD-1+ T cells were analyzed using flow cytometry. Results The percentages of CD4+PD-1+ as well as CD8+PD-1+ T cells in the psoriatic patients both with and without arthritis were significantly lower than in the control group. The percentages of CD4+PD-1+ as well as CD8+PD-1+T cells were not significantly different between the psoriatic patients with and without arthritis. A significant positive correlation between PD-1 expression on the CD4+ and CD8+ T cells was found in the psoriatic patients without arthritis. Conclusions Impairment of the negative co-stimulation from PD-1 may be another common characteristic of psoriasis both with and without arthritis.