Mathematical model of proliferative activity in epidermis of the normal skin and of the skin afflicted by psoriasis

A mathematical model of the mitotic activity of epidermis in norm and psoriasis is presented, which consists of a system of two autonomous nonlinear differential equations. A qualitative analysis of the model was done, and numerical solutions at the parameter values corresponding to these state were obtained. It was shown that, in norm, the system can exist only in one stationary equilibrium state of the "focus" type, and in psoriasis, due to an increase in the growing fraction, hyperproliferation, and enhanced migration of keratinocytes, a stable limiting cycle arises from the state of an unstable focus. The existence of two stable states (focus and the limiting cycle) is regulated by a parameter that describes the inhibition of division of maturing cells of suprabasal epidermal layers by the intrinsic tissue-specific transmitters of mitosis of G1-keilon type. The model is consistent with experimental data on the kinetics of cell proliferation in the epidermis in norm and psoriasis and the clinical course of the disease.     

Mutual synchronization of cell density auto-oscillations in psoriatic skin lesions in a model of paracrine regulation of epidermal proliferation involving T lymphocytes

A computer simulation study is made on mutual synchronization of auto-oscillations of epidermal cell density in psoriatic skin lesions under conditions of strong clipped noise. The initial model is a system of three ordinary nonlinear differential equations, presumably describing the principles of paracrine regulation of epidermal proliferation with functionally activated CD4+/CD8+ lymphocytes. It is shown that, if epidermal proliferation is considered as an attribute determining the pathomorphological features of dermatoses, synchronization may prove responsible for development of linear, annular, arcuate, geographical psoriasis, and also the restricted and the disseminated forms of disease. It is shown that strong noise can shift the time of clinical manifestation of ensembles of synchronized psoriatic lesions by several days; the phase slip, up to tens of days; and differences in physical parameters, by several hours to several days.     

Stability of synchronization clusters and seizurability in temporal lobe epilepsy

Purpose

Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the “epileptic focus model”, localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes.

Methods

The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results. Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery.

Discussion

We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases.     

S100A7: A rAMPing up AMP molecule in psoriasis

S100A7 (psoriasin), an EF-hand type calcium binding protein localized in epithelial cells, regulates cell proliferation and differentiation. An S100A7 overexpression may occur in response to inflammatory stimuli, such in psoriasis, a chronic inflammatory autoimmune-mediated skin disease. Increasing evidence suggests that S100A7 plays critical roles in amplifying the inflammatory process in psoriatic skin, perpetuating the disease phenotype. This review will discuss the interactions between S100A7 and cytokines in psoriatic skin. Furthermore, we will focus our discussion on regulation and functions of S100A7 in psoriasis. Finally, we will discuss the possible use of S100A7 as therapeutic target in psoriasis.     

Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans

Herein, we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n = 3) were compared with littermate controls (n = 3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average p = 0.0082; cystatin A, human ortholog); slc25a5 (average fold change of 46.2 and an average p = 0.0318); serpinb3b (average fold change of 35.6 and an average p = 0.0345; serpinB1, human ortholog); and kallikrein related peptidase 6 (average fold change of 4.7 and an average p = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, p < 0.0001), KLK6 (9-fold, p = 0.002), stefin A1 (7.3-fold; p < 0.001), and slc25A5 (1.5-fold; p = 0.05) using qRT-PCR on a second cohort of animals (n = 8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; p < 0.05), 29,000-fold (stefinA1; p < 0.01), 322-fold (KLK6; p < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes versus healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3-fold), KLK6 (5.8-fold), and serpinB1 (76-fold; all p < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover, slc25a5, cystatin A, KLK6, and serpinB1 protein were all increased in lesional psoriasis skin compared with normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.One in three individuals in the United States is afflicted with a skin disease, with ∼2–3% of the American population suffering from psoriasis (1–3) a chronic, immune-mediated inflammatory skin disease characterized by well-demarcated areas of “involved” red, raised, and scaly skin adjacent to areas of “uninvolved” normal appearing skin. The underlying cause of psoriasis remains unknown and the specific signals that trigger disease onset have yet to be identified; however, several lines of evidence suggest the involvement of antigen-specific T cells, although the antigens involved remain elusive (4). A combination of human and animal studies have led to the understanding that in patients with a genetically susceptible background, some initiating stimulus, often a stressful event, an injury to the skin, or an infection, leads to a coordinated series of signaling events involving cytokines, resident skin cells, and skin-infiltrating immune cells, that once started, initiates a vicious pro-inflammatory hyperproliferative cycle. Once initiated, this cycle perpetuates sustained inflammatory responses. Intervention at several points in this cycle results in clinical resolution, however, durable remission and/or permanent clearance has not yet been achieved.Current psoriasis therapies are directed toward symptomatic relief and none of them represent a cure for this chronic illness. Current treatments include topical therapies, phototherapy, and systemic administration of immune-suppressants, anti-metabolites, oral retinoids, and biologics targeting immune cells or inflammatory cytokines (5, 6). Many of the most effective therapeutics however, also have the greatest adverse reactions; moreover, psoriasis can become resistant to specific therapies over time. Therefore, an ongoing need for discovery of new biological pathways and targets for psoriasis is obvious.We studied a mouse model of psoriasis using an unbiased proteomics screening approach to identify dysregulated peptides of interest in psoriasiform-inflamed mouse skin and ultimately compared these findings to psoriasis patient skin. We used in-gel label-free protein expression analysis to observe quantitative changes in protein expression. The peptides that were determined to be top-scoring from a statistical perspective and of biological interest were subjected to further analysis and confirmation using a targeted mass spectrometry approach along with qRT-PCR to assess gene expression in a distinct set of animal samples. Further validation of the translational importance of these novel proteins was then conducted in primary keratinocytes expanded from psoriasis skin as well as human skin taken directly from psoriasis patient lesional and nonlesional areas. The results of these experiments confirm the ability of a discovery in-gel label-free expression model to identify proteins that are in the moderate to high abundance range that are significantly different in their distribution between control and genetically modified psoriasiform mouse skin and demonstrate the usefulness of mouse models and proteomic approaches for identifying novel proteins that are differentially regulated in human psoriasis, providing future biomarkers and targets for development of translational approaches to disease improvement.     

Trigger factors in childhood psoriasis and vitiligo

Psoriasis and vitiligo are very common skin disorders that may have a profound impact upon the affected individuals; the etiology of both diseases includes genetic factors and triggers, which could be endogenous or exogenous. Two groups of children population consisting of 153 patients suffering from skin disorder (65 with vitiligo and 88 with psoriasis) have been examined at the Department of Dermatovenerology, University Hospital Osijek, during three years period. Basic methods of data collection were: questionnaire, clinically examination and histological proven diagnosis. The aim of this investigation were to determine the most common triggers, which play a role at onset of disease among young patients with vitiligo and psoriasis, and to establish familial distribution among both groups of patients. The results of investigations showed that the onset of vitiligo was mostly connected with psychological factors (56.9%), but the most frequently trigger in childhood psoriasis was inflammatory focus (38.6%). According to morphologic patterns the authors separated two groups of patients among psoriatics: group I with plaque psoriasis, which pointed the inflammatory focus and physical trauma as trigger before onset of disease (each 25.0%) and group II with psoriasis guttata and inflammatory focus as trigger at even 62.5% cases. Familial distribution among psoriatic children was 55.6%, and among children with vitiligo only 16.9%. Ours children patients showed significantly disparity in structure of triggers according diagnosis and gender distributions and about familial occurrence. Also some difference has been established according to age of onset between psoriasis and vitiligo at early childhood.     

IMQ Induced K14-VEGF Mouse: A Stable and Long-Term Mouse Model of Psoriasis-Like Inflammation

An imiquimod (IMQ) induced wild type (WT) mouse can mimic some features of psoriasis, such as thickened skin, abnormal keratinocyte-related proteins, infiltration of inflammatory cells and pro-inflammatory cytokines. This model is a prevalent model that is widely used in the study of psoriasis. However, skin inflammation decreases during the eighth day when IMQ is given to WT mice, which may result in false results when evaluating the pharmacodynamics effects of a drug. To extend the timeliness and inherit the advantages of this model, we applied IMQ to the skin of 8-week-old homozygous K14-VEGF mice to investigate whether IMQ can prolong mice ear inflammation. In our experiments, we found that, compared to the IMQ induced WT mice model, the IMQ induced K14-VEGF mice have serious skin inflammation, even on the fourteenth day. We also evaluated the stability of skin inflammation at days 8, 10, and 13, and the inflammatory situation remained stable in the skin. This research intends to improve the existing model, and we hypothesize that the IMQ induced K14-VEGF mouse will become a practical mouse model in psoriasis research.     

A simple method for the evaluation of epidermal thickness variations in psoriasis vulgaris

OBJECTIVE: To evaluate the "variation" of the epidermal thickness and variables such as the mean, maximum, and minimum thickness for the diagnosis and follow-up of some skin diseases such as psoriasis. STUDY DESIGN: A simple quantitative method is described. A series of psoriasis vulgaris cases is provided as an example. Biopsy samples taken before and after topical treatment were used. RESULTS: The mean thickness was higher in lesions compared to the perilesional control skin (p < 0.001) and post-treatment lesional area (p < 0.001). CONCLUSION: The thickness of the epidermis varies due to a multitude of factors. Measuring the mean epidermal thickness may be important. However, this measurement may not be the best way for studies involving a series of patients and a variety of lesion sites. The natural variations in the thickness of the epidermis of different body sites and of different persons may prevent the usage of thickness measurements alone on a wider scale. It is hoped that this method can be used for evaluation of certain skin diseases affecting epidermal thickness where variation of the epidermal thickness is a potentially useful diagnostic and therapeutic variable.     

Cytokines in psoriasis

Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis.     

CD57 Expression and Cytokine Production by T Cells in Lesional and Unaffected Skin from Patients with Psoriasis

Background

The immunopathogenic mechanisms leading to psoriasis remain unresolved. CD57 is a marker of replicative inability and immunosenescence on CD8+ T cells and the proportion of CD57 expressing CD8+ T cells is increased in a number of inflammatory conditions.

Methodology

We examined the expression of CD57 on T cells in the skin of patients affected with psoriasis, comparing lesional and unaffected skin. We also assessed functionality of the T cells by evaluating the secretion of several inflammatory cytokines (IL-17A, IFN-gamma, IL-2, IL-33, TNF-alpha, IL-21, IL-22, and IL-27), from cell-sorted purified CD4+ and CD8+ T cells isolated from lesional and unaffected skin biopsies of psoriasis patients.

Principal Findings

We observed that the frequency of CD57+CD4+ and CD57+CD8+ T cells was significantly higher in unaffected skin of psoriasis patients compared to lesional skin. Sorted CD4+ T cells from psoriatic lesional skin produced higher levels of IL-17A, IL-22, and IFN-gamma compared to unaffected skin, while sorted CD8+ T cells from lesional skin produced higher levels of IL-17, IL-22, IFN-gamma, TNF-alpha, and IL-2 compared to unaffected skin.

Conclusions/Significance

These findings suggest that T cells in unaffected skin from psoriasis patients exhibit a phenotype compatible with replicative inability. As they have a lower replicative capacity, CD57+ T cells are less frequent in lesional tissue due to the high cellular turnover.     

The gut microbiota profile in psoriasis: a Brazilian case-control study

The pathogenesis of psoriasis, an immune-mediated chronic inflammatory skin disease, remains unclear. Studies have shown an association between psoriasis and intestinal inflammation; in this context, the influence of the gut microbiota on the immune response of psoriasis has become a focus of recent research. The present research evaluated the composition and diversity of the gut microbiota of 21 participants with psoriasis from a Brazilian referral dermatology service compared to 24 healthy controls. A stool sample was collected from each participant at the time of inclusion in the study, and the samples were analysed by sequencing the 16S rRNA gene. The recruitment of research participants involved matching between groups by sex, age, body mass index, comorbidities and smoking and the exclusion of several criteria that could potentially influence the gut microbiota and the interpretation of the data. There was an increase in the Dialister genus and Prevotella copri species in patients with psoriasis compared to the control group. A reduction in the Ruminococcus, Lachnospira and Blautia genera, as well as in the Akkermansia muciniphila species, was also verified in the psoriasis group compared to the control group. Furthermore, patients with psoriasis exhibited less gut microbiota diversity than controls.     

Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers

Background

Psoriatic arthritis (PsA) is a distinct inflammatory arthritis occurring in 30% of psoriasis patients. There is a high prevalence of undiagnosed PsA in psoriasis patients; therefore, identifying soluble biomarkers for PsA could help in screening psoriasis patients for appropriate referral to a rheumatologist. Potential PsA biomarkers likely originate in sites of inflammation, such as the skin, and subsequently enter systemic circulation. Our goal was to identify candidate PsA biomarkers by comparing the proteome of skin biopsies obtained from patients with PsA to that from patients with psoriasis without PsA.

Methods

Skin biopsies were obtained from involved and uninvolved skin of 10 PsA and 10 age/gender-matched psoriasis patients without PsA (PsC). Using strong cation exchange chromatography, followed by label-free quantitative tandem mass spectrometry, we characterized the proteomes of pooled skin samples. Extracted ion current intensities were used to calculate protein abundance ratios, and these were utilized to identify differentially regulated proteins.

Results

Forty-seven proteins were elevated in PsA-derived skin compared to PsC-derived skin. Selected reaction monitoring assays were developed to quantify these potential PsA markers in individual skin samples, and 8 markers were confirmed in an independent sample set. ITGB5 and POSTN were measured in serum samples from 33 PsA and 15 PsC patients, using enzyme-linked immunosorbent assays. ITGB5 was significantly elevated in PsA serum (P < 0.01), and POSTN showed a trend. ITGB5 and POSTN correlated significantly in both patient groups (r = 0.472, P < 0.001).

Conclusion

Proteomic analysis of PsA and PsC skin identified eight new candidate biomarkers. These markers need to be validated with a larger and independent cohort, in order to delineate their clinical utility in PsA patients. These proteins may also uncover unknown aspects of PsA pathobiology.

Electronic supplementary material

The online version of this article (doi:10.1186/1559-0275-12-1) contains supplementary material, which is available to authorized users.     

Skin microbiota of first cousins affected by psoriasis and atopic dermatitis

Background

Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin diseases, which negatively influence the quality of life. In the last years, several evidences highlighted the pivotal role of skin bacteria in worsening the symptomatology of AD and psoriasis. In the present study we evaluated the skin microbiota composition in accurately selected subjects affected by (AD) and psoriasis.

Methods

Three first cousins were chosen for the study according to strict selection of criteria. One subject was affected by moderate AD, one had psoriasis and the last one was included as healthy control. Two lesional skin samples and two non-lesional skin samples (for AD and psoriatic subjects) from an area of 2 cm² behind the left ear were withdrawn by mean of a curette. For the healthy control, two skin samples from an area of 2 cm² behind the left ear were withdrawn by mean of a curette. DNA was extracted and sequencing was completed on the Ion Torrent PGM platform. Culturing of Staphylococcus aureus from skin samples was also performed.

Results

The psoriatic subject showed a decrease in Firmicutes abundance and an increase in Proteobacteria abundance. Moreover, an increase in Streptococcaceae, Rhodobacteraceae, Campylobacteraceae and Moraxellaceae has been observed in psoriatic subject, if compared with AD individual and control. Finally, AD individual showed a larger abundance of S. aureus than psoriatic and healthy subjects. Moreover, the microbiota composition of non-lesional skin samples belonging to AD and psoriatic individuals was very similar to the bacterial composition of skin sample belonging to the healthy control.

Conclusion

Significant differences between the skin microbiota of psoriatic individual and healthy and AD subjects were observed.

     

IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus

Background

SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.

Objectives

Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).

Results

SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.

Conclusions

These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.     

Oxidative stress involvement in psoriasis: a systematic review

Psoriasis is a skin chronic inflammatory disease with a complex aetiology. It is characterised by the imbalance of environmental, genetic, and immunologic factors. Reactive oxygen species (ROS) could damage the cell components. The antioxidant system defends the body against ROS; a malfunction of the antioxidant system, together with an increased production of ROS, is involved in the pathogenesis of several diseases such as psoriasis. The purpose of this systematic review is to give an updated scenario about oxidative stress involvement in the psoriatic disease to identify useful biomarkers and to propose innovative therapies. A total of 28 studies were identified. Although several molecules were demonstrated being associated with psoriasis, only a little group resulted being eligible as disease biomarker [malonyldialdehyde (MDA), total oxidative stress, and oxidative stress index]. However, only MDA seems to be the best candidate for a clinical screening of psoriasis patients since it is intimately linked to Psoriasis Area Severity Index. Data suggest that current therapies with drugs, a healthy lifestyle, and the integration of a diet rich in antioxidants help to reduce the damage of oxidative stress caused by psoriasis, especially at the level of the skin. As much as we know, this is the first systematic review evaluating the oxidative stress role in psoriasis.     

Identification of cellular pathways of "type 1," Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis

Therapeutic modulation of psoriasis with targeted immunosuppressive agents defines inflammatory genes associated with disease activity and may be extrapolated to a wide range of autoimmune diseases. Cyclosporine A (CSA) is considered a "gold standard" therapy for moderate-to-severe psoriasis. We conducted a clinical trial with CSA and analyzed the treatment outcome in blood and skin of 11 responding patients. In the skin, as expected, CSA modulated genes from activated T cells and the "type 1" pathway (p40, IFN-gamma, and STAT-1-regulated genes). However, CSA also modulated genes from the newly described Th17 pathway (IL-17, IL-22, and downstream genes S100A12, DEFB-2, IL-1beta, SEPRINB3, LCN2, and CCL20). CSA also affected dendritic cells, reducing TNF and inducible NO synthase (products of inflammatory TNF- and inducible NO synthase-producing dendritic cells), CD83, and IL-23p19. We detected 220 early response genes (day 14 posttreatment) that were down-regulated by CSA. We classified >95% into proinflammatory or skin resident cells. More myeloid-derived than activated T cell genes were modulated by CSA (54 myeloid genes compared with 11 lymphocyte genes), supporting the hypothesis that myeloid derived genes contribute to pathogenic inflammation in psoriasis. In circulating mononuclear leukocytes, in stark contrast, no inflammatory gene activity was detected. Thus, we have constructed a genomic signature of successful treatment of psoriasis which may serve as a reference to guide development of other new therapies. In addition, these data also identify new gene targets for therapeutic modulation and may be applied to wide range of autoimmune diseases.     

Elevated interleukin-18 protein expression in early active and progressive plaque-type psoriatic lesions

Psoriasis is a T cell-mediated inflammatory skin disease characterized by an elevated IFN-gamma and IL-12p70 expression in skin lesions. Interleukin-18 (IL-18) synergizes with IL-12 to induce IFN-gamma production and a strong T-helper-1-mediated immune response, or to induce Th2 polarization depending on the immunological context. We have previously shown that keratinocytes in normal skin produce and store large amounts of pro-IL-18. In this study, we hypothesized that the expression of IL-18 in psoriatic lesional skin might be altered compared to normal skin. Therefore, IL-18 expression was assessed in psoriatic, stable, plaque-type lesions and early active and progressive lesions. IL-18 mRNA and protein concentrations were constitutively high, and did not differ between normal and stable, plaque-type epidermis. In active and progressive lesions an elevated expression of total IL-18 protein relative to normal and stable, plaque-type epidermis was detected using ELISA, while on Western blot, the differences in pro- or mature IL-18 were less clear. Our results indicate that the role of IL-18 in the pathogenesis of early phases of psoriasis may be more prominent than in established psoriatic lesions.