Lenka Borska

Serum levels of the pro‐inflammatory cytokine interleukin‐12 and the anti‐inflammatory cytokine interleukin‐10 in patients with psoriasis treated by the Goeckerman regimen

Background  The Goeckerman regimen (GR) involves the dermal application of a crude coal tar (polycyclic aromatic hydrocarbon, PAH) and exposure to ultraviolet (UV) radiation. Both PAH and UV radiation exhibit immunosuppressive activity. This study describes the changes in the serum levels of the pro‐inflammatory cytokine interleukin‐12 (IL‐12) and the anti‐inflammatory cytokine IL‐10 in patients with psoriasis (n = 55) treated with GR.

Immunologic Changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in Pediatric Patients Treated for Psoriasis with the Goeckerman Regimen

Abstract:  Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF‐alpha and adhesion molecules sICAM‐1, sP‐selectin and sE‐selectin decreased after the Goeckerman regimen. The TNF‐alpha and sICAM‐1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL‐8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL‐8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

Background  Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar [polycyclic aromatic hydrocarbons (PAH)] and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis.

Genotoxic Hazard and Cellular Stress in Pediatric Patients Treated for Psoriasis with the Goeckerman Regimen

Abstract:  The Goeckerman regimen (GR) represents a local treatment of psoriasis and includes topical dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV‐irradiation. The aim of the study was to evaluate contribution of GR to genotoxic risk and cellular stress in pediatric patients who represent a sensitive population subgroup. Genotoxic risk (42 patients) was evaluated by using chromosomal aberrations (CA) in peripheral lymphocytes. Cellular stress (26 patients) was assessed by using heat shock proteins (Hsp70). All indicators were determined in blood samples collected before GR and immediately after GR. Decreasing of psoriasis area and severity index (PASI) score indicated higher likelihood of GR (p < 0.001). Significantly increased CA (p < 0.001) and Hsp70 (p < 0.05) indicated higher genotoxic risk and cellular stress in sensitive pediatric patients, immediately after GR.

CC and CXC chemokines patterns in psoriasis determined by protein array method were influenced by Goeckerman's therapy.

Goeckermans therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. The aim of this study was to evaluate the influence of Goeckermans therapy of psoriasis on the levels of proangiogenic chemokines ENA-78 (CXCL5, Epithelial Cell Derived Neutrophil Attractant-78), GRO alpha (CXCL1, Growth-Related Oncogene), IL-8 (CXCL8, Interleukin-8), MCP-1 (CCL2, Monocyte Chemotactic (Chemoattractant) Protein 1) and RANTES (CCL5, Regulated on Activation of Normal T Cell Expressed and Secreted) in peripheral blood of 22 childrens patients with psoriasis. 22 otherwise healthy children serve as a control group. The serum levels of chemokines were determined by commercial membrane protein array technique (RayBiotech, USA). Efficacy of Goeckermans therapy was delineated by PASI score. Disease activity was significantly diminished by Goeckermans therapy (p < 0.001). Serum levels of GRO alpha and MCP-1 in patients before GT were significantly higher than those measured in healthy blood donors (GRO alpha: p = 0.0128 and MCP-1: p = 0.0003). Serum levels of GRO alpha, MCP-1 and RANTES were significantly diminished by GT (GRO alpha: p = 0.002, MCP-1: p = 0.048 and RANTES: p = 0.0131). Compared to the healthy controls, serum level of MCP-1 remained significantly increased in psoriasis patients after GT (p < 0.0001). In conclusion, we found that the GT of psoriasis influenced the serum levels of proinflammatory and proangiogenic chemokines, especially GRO alpha, MCP-1 and RANTES. It could be the cause for decreased proangiogenic activity which is described after GT of psoriasis.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

BACKGROUND Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

Metabolic Syndrome and Selective Inflammatory Markers in Psoriatic Patients

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (p < 0.05) and diastolic blood pressure (p < 0.05) in the psoriatic patients. The values of waist circumference and BMI were significantly higher (p < 0.05) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP (p < 0.001), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.01) levels in the psoriatic patients. Significantly higher levels of CRP (p < 0.01), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.05) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower (p < 0.01) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 (p < 0.001) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients.

Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

Serum Level of Antibody against Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA Adducts in People Dermally Exposed to PAHs

Some specific antibodies indicate the presence of antigenic structures on DNA (DNA adducts) that can play an important role in the process of mutagenesis and/or carcinogenesis. They indicate the presence of increased genotoxic potential (hazard) prior to the formation of disease (primary prevention). The present study was focused on the serum level of benzo[a]pyrene 7,8-diol-9,10-epoxide-DNA adducts antibodies (anti-BPDE-DNA) in psoriatic patients (n = 55) dermally exposed to different levels of polycyclic aromatic hydrocarbons (PAHs). The general goal of the study was to contribute to better understanding of the value of the assumed biomarker (anti-BPDE-DNA) for evaluation of the organisms answer to genotoxic exposure to PAHs. Elevated level of exposure to PAHs resulted in the increased level of anti-BPDE-DNA. However, almost all levels of anti-BPDE-DNA ranged within the field of low values. Both variants of GT (CCT-3% and CCT-5%) induced higher expression of anti-BPDE-DNA in the group of nonsmokers. Significant relations between the level of anti-BPDE-DNA and PASI score, total duration of the therapy, or time of UVR exposure were not found. Further studies are needed to reduce interpretation uncertainty of this promising bioindicator.

Membrane and soluble Toll-like receptor 2 in patients with psoriasis treated by Goeckerman therapy

Toll‐like receptor (TLR) 2 belongs to the large TLR receptor family comprised of at least 10 members with different roles in innate immunity. Psoriasis is recognized as a T‐cell driven immune‐mediated systemic inflammatory disease with a skin manifestation. An effective therapeutic approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to assess both the kinetics of the expression of TLR2 on blood cells and the concentration of soluble (s)TLR2 in serum of patients with psoriasis and to examine the effect of GT on both TLR2 expression and sTLR2 level.