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Effect of narrow-band ultraviolet B on the level of interleukin-17 in psoriasis patients

El Shiemy, Saleh M.a; Abd Allah, Marwa A.a; Abd Allah, Tarek N.b; El Fangary, Mona M.b; Saudi, Wael M.b; Sayed, Ahmed M.b

Journal of the Egyptian Women's Dermatologic Society: May 2013 - Volume 10 - Issue 2 - p 85–88
doi: 10.1097/01.EWX.0000430953.49521.93
Original articles
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Background Psoriasis is a chronic inflammatory skin disease that is thought to be mediated by T helper (Th1) cells. Interestingly, recent advances by cellular immunologists have led to the identification of a new distinct type of T cell called Th17 cells that may play an essential pathogenic role in psoriasis.

Objective The present study was planned to study the effect of narrow-band ultraviolet B (NB-UVB) on serum levels of interleukin-17 (IL-17) in psoriasis patients.

Patients and methods In this study, we estimated serum levels of IL-17 in 20 psoriatic patients before and after 36 sessions of NB-UVB and in 10 healthy controls using enzyme-linked immunosorbent assay, correlating their levels with disease severity, which was calculated using the psoriasis area severity index.

Results The mean serum levels of IL-17 were significantly elevated in patients with psoriasis in comparison with those in normal controls. Moreover, there was significant elevation in mean serum IL-17 levels of psoriatic patients before treatment compared with those after treatment.

Conclusion Psoriasis is a Th1 and Th17-mediated inflammatory skin disease, and NB-UVB has a significant inhibitory effect on both serum levels of IL-17 and psoriasis area severity index scores.

aDepartment of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo

bDepartment of Dermatology and Venereology, Faculty of Medicine, Misr University for Science and Technology (MUST), Giza, Egypt

Correspondence to Wael M. Saudi, MD, Department of Dermatology and Venereology, Faculty of Medicine, Misr University for Science and Technology, 12582 Cairo, Egypt Tel: +20 114 836 0036; e-mail: waelsaudi70@yahoo.com

Received January 20, 2013

Accepted March 12, 2013

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Introduction

Psoriasis is a complex inflammatory skin disease that affects 2.3% of the population worldwide. Although the initial events triggering a psoriatic lesion are still unknown 1, they activate dendritic cells, such as Langerhans cells, inducing their migration to skin-draining lymph nodes. Here, antigen-specific T cells are primed by the migrated skin dendritic cells to differentiate into effector T cells, which then traffic to the skin where, together, they induce the formation of a primary psoriatic plaque. During this step, some T cells and dendritic cells start to infiltrate the epidermis, releasing proinflammatory cytokines, which in turn stimulate keratinocyte proliferation 2.

Psoriasis can be considered a T-cell-mediated disease, with a complex role for a variety of cytokine interactions between keratinocytes and T lymphocytes. T helper cells were initially divided into Th1 and Th2 subsets but now also include a new subset called Th17 cells 3.

The identification of the Th17 subset has now broadened our understanding of inflammatory processes in human disease, which through the production of both interleukin-17 (IL-17) and IL-22, induction of chemokines, and recruitment of other effector cell populations might have essential function in the pathogenesis of psoriasis 4.

The main effect of IL-17 is the recruitment and activation of neutrophils. IL-17 also enhances angiogenesis and mediates tissue remodeling by stimulating the production of angiogenic factors and matrix metalloproteases. In addition, IL-17A synergizes with tumor necrosis factor-α (TNF-α) to enhance inflammation, causing the release of IL-6, TNF-α, and IL-1β. Finally, IL-17A can directly activate keratinocytes to express the granulocyte macrophage colony-stimulating factor IL-6 and a variety of chemokines and adhesion molecules 5.

In 1981, Parrish and Jaenicke 6 reported that the 311 nm wavelength of ultraviolet B (UVB) radiation, called narrow-band ultraviolet B (NB-UVB), was the most effective and least erythemogenic among the UVB levels in the treatment of psoriasis. UVB irradiation inhibits cutaneous delayed-type hypersensitivity responses to haptens, and its therapeutic mechanism in psoriasis has been attributed to these immunosuppressive properties. Interestingly, irradiation of psoriatic skin lesions with standard UVB light causes rapid depletion of intraepidermal T cells. As apoptosis is induced by in-vitro UVB irradiation of T cells, it has been proposed that UVB may have immunosuppressive effects in psoriasis through induction of apoptosis in disease-mediating T cells 7.

However, although it is clear that NB-UVB can suppress inflammatory cytokines, it is still unproved whether it can similarly target pathogenic IL-17 production. Therefore, the present study was planned to assess the effect of NB-UVB on serum levels of IL-17 in psoriasis patients.

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Patients and methods

Patients

This study included 20 patients with psoriasis vulgaris and 10 normal controls recruited from the Dermatology outpatient clinic of Ain shams University Hospital and of Misr University for Science and Technology (MUST) hospital during February 2011 to August 2011. Informed consent was obtained from patients after approval from the Research Ethics Committee before the study.

Patients were diagnosed clinically, and their disease severity was measured using psoriasis area severity index (PASI). They were divided according to their pretreatment PASI scores into three subgroups: those with a PASI score less than 20 were considered having mild disease, those with scores between 21 and 50 as having moderate disease, and those with scores above 50 were considered as having severe disease. They were treated at the Ultraviolet Therapy Unit of both hospitals with NB-UVB. Sessions were performed three times a week for a total 36 sessions. The initial therapeutic dose was 75% of the minimal erythema dose and was incremented by 20% of the previous dose if no erythema was induced. The inclusion criteria included not receiving any topical or systemic therapy for psoriasis at least 1 month before the study. The exclusion criteria included having any history of other autoimmune diseases. PASI-75, PASI-50 which are the percentage of patients that achieved 75%, 50% reduction in their baseline PASI, respectively, were used in determining the efficacy of NB-UVB.

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Serum collection

Serum samples were obtained from all patients before and after the 36 sessions of NB-UVB and once from controls. Venous blood samples of 3 ml were collected in sterile plane tubes and were allowed to stand for 30 min at room temperature, they were then centrifuged at 300g for 5 min. Sera were immediately separated and stored at −60°C until analysis.

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IL-17 estimation

The kit used in our study was the antihuman IL-17 (primary antibody) (IDELISA kit; IDlabs Biotechnology, London, Ontario, Canada).

IL-17 levels in serum were estimated using a solid-phase sandwich enzyme-linked immunosorbent assay. It utilizes a monoclonal antibody (capture antibody) specific for human IL-17 coated onto a 96-well plate. Standards and samples were added to the wells, and any human IL-17 present will bind to the immobilized antibody. The wells were washed, and the biotinylated polyclonal antihuman IL-17 antibody (detection antibody) was added. After a second wash, avidin–horseradish peroxidase was added producing an antibody–antigen–antibody sandwich. The wells were washed again, and a substrate solution was added, which produced a blue color in direct proportion to the amount of human IL-17 present in the initial sample. The stop buffer was then added to terminate the reaction. This reaction results in a color change from blue to yellow. The wells are then read at 450 nm.

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Statistical analyses

Statistical analyses were performed using statistical package for social science (SPSS15.0.1 for windows; SPSS Inc., Chicago, Illinois, USA). Numerical data were expressed as mean±SD and as median and range, whereas non-numerical data were expressed as frequency and percentage. Student’s t-test was used to assess the statistical significance of the difference between the mean values of two study groups. The analysis of variance test was used to study the statistical significance of the difference between the mean values of more than two groups. Correlation analysis (using Pearson’s method) was used to assess the strength of association between two quantitative variables. The correlation coefficient denoted symbolically as ‘r’ defines the strength and direction of the linear relationship between two variables. A P-value of 0.05 or less was considered significant.

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Results

Psoriatic patients were divided according to their pretreatment PASI scores into three subgroups: mild (10 patients, 50%), moderate (five patients, 25%), and severe (five patients, 25%). All patients showed a significant decrease in their PASI scores: 15 patients achieved PASI scores of 75, two patients achieved PASI scores of 50, and the remaining three patients achieved PASI scores less than PASI 50.

There was a significant difference in the levels of serum IL-17 between the three groups, wherein the mild form showed the highest level, followed by the moderate and then the severe type (Table 1).

Table 1

Table 1

Serum levels of IL-17 of patients and controls are shown in Table 2. There was a highly significant difference in mean serum IL-17 levels between patients before treatment and controls, with a higher level of IL-17 among patients (P<0.001). There was no significant difference in mean IL-17 levels between patients after treatment and controls (P>0.05).

Table 2

Table 2

There was a highly significant difference between the levels in patients before and after treatment, with a higher level of IL-17 among patients before treatment (P<0.05).

There was a negative correlation between the level of IL-17 and the PASI score in the studied psoriasis patients before treatment as shown in Fig. 1; however, this correlation was not significant (r=−0.343, P>0.05).

Figure 1

Figure 1

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Discussion

Psoriasis vulgaris is a chronic relapsing hyperproliferative skin disease characterized histologically by acanthosis, parakeratosis, and dermal infiltration of mononuclear cells such as T cells, dendritic cells, and monocytes/macrophages 2. All these cells, given their ability to link the innate and acquired immune systems and to regulate cytokine production, seem to contribute to establish psoriatic lesions 8.

T cells involved in psoriasis pathogenesis were initially thought to be Th1 differentiated because of the presence of elevated levels of interferon-γ (IFN-γ) in psoriatic patients 9. Psoriatic skin contains a T-cell infiltrate, with a significantly increased percentage of Th17 cells and the ability to produce IL-17 alone or in combination with IL-22. This indicates that this subset either shows a preferential homing to the lesions in psoriasis patients or proliferates after being activated, possibly as a result of recognition of locally presented antigen(s) 10.

In this study, serum IL-17 levels were measured using enzyme-linked immunosorbent assay from the sera of 20 psoriatic patients and 10 normal controls. PASI scores were estimated in the 20 psoriatic patients. The results demonstrated that mean serum levels of IL-17 were significantly elevated in patients with psoriasis in comparison with normal controls. Similarly, Takahashi et al.11 reported that mean serum levels of IL-17 were significantly increased in patients with psoriasis when compared with healthy controls.

On comparing mild, moderate and severe psoriasis according to the PASI score, a significant difference was found in the present study. The estimated IL-17 levels were surprisingly highest in patients with mild and lowest in patients with severe psoriasis, considering all were higher compared with those in healthy controls. However, we found a nonsignificant negative correlation between PASI scores and IL-17 levels. Our results are consistent with those of Kagami et al.12, who reported that serum levels of IL-17 are increased in psoriatic patients when compared with normal individuals; however, this elevation did not correlate with disease severity.

This observation may be explained by the fact that proinflammatory cytokines are usually more active and elevated at sites of tissue inflammation than in circulation 12. As the high levels of IFN-γ in psoriatic lesions can downregulate IL-17 production 13, IL-17 may not be involved in determining the severity of psoriasis, unlike IL-22, which increases in psoriatic lesions and in plasma of psoriasis patients, and these levels correlate with disease severity 14.

Our results were different from those of Almakhzangy and Gaballa 15, who reported that serum levels of IL-17 were significantly correlated with the PASI score. In addition, the results of the present study were different from those obtained by Arican et al.16, who stated that IL-17 levels of patients were not significantly higher compared with those of controls and that there was a significant correlation between serum levels of IL-17 and disease severity.

All patients were treated by NB-UVB for 36 sessions, and this was accompanied by an improvement in disease severity, a significant decrease in PASI scores, and a significant decrease in serum IL-17 levels (P<0.001). Therefore, the decreases in PASI scores after NB-UVB therapy in the three groups indicate that NB-UVB effectively treats psoriasis, proving the role of NB-UVB in reducing cytokine levels. NB-UVB therapy has many immunosuppressive effects: it leads to a reduction in the number of T cells by inducing apoptosis, decreasing the number of Langerhans cells after therapy, and decreasing Th1 cytokine levels 17. Piskin et al.18 reported that treatment with NB-UVB causes a significant decrease in PASI scores and in levels of IFN-γ and other Th1 cytokines.

The results of the present study were compatible with those of Vähävihu et al.19, who reported that NB-UVB caused a marked but nonsignificant reduction of IL-17 in psoriasis lesions. Johnson-Huang et al.20 reported that NB-UVB suppresses the IL-23/IL-17 axis in normalized psoriatic plaques.

Coimbra et al.21 reported that both NB-UVB and psoralen plus UVA (PUVA) treatments produced significant reductions in levels of IL-22, IL-17, IL-23, IL-8, TNF-α, and vascular endothelial growth factor, reflecting the observed improvement in the lesions and reduction in proinflammatory signals.

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Conclusion

We provided further evidence for elevation of IL-17 levels in the circulatory system of psoriatic patients and that its concentration is in negative correlation with disease severity and decreases with administration of NB-UVB therapy.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

narrow-band ultraviolet B; psoriasis; serum interleukin-17

© 2013 Egyptian Women's Dermatologic Society