|Year : 2015 | Volume
| Issue : 2 | Page : 387-391
The role of leptin in the pathogenesis of psoriasis
H Maree Alaa1, A Khodeer Seham2, A ELTahmoudy Mohamad3, G Farag Azza1, F EL Semlawy Mohamed MD 1
1 Department of Dermatology and Sexually Transmitted Diseases, Faculty of Medicine, Menoufiya University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufiya University, Cairo, Egypt
3 Department of Pathology, Faculty of Medicine, Menoufiya University, Cairo, Egypt
|Date of Submission||24-Mar-2014|
|Date of Acceptance||24-May-2014|
|Date of Web Publication||31-Aug-2015|
F EL Semlawy Mohamed
Dermatology and Sexually Transmitted Diseases Department, Faculty of Medicine, Menoufiya University, Cairo
Source of Support: None, Conflict of Interest: None
To clarify the role of leptin in the pathogenesis of psoriasis.
Psoriasis is considered a systemic disease with significant cardiovascular comorbidity. Studies suggested that hyperleptinemia might play an important role in obesity-associated cardiovascular diseases, including atherosclerosis.
The study included 40 consecutive patients with plaque-type psoriasis and 10 control individuals The patients were recruited from the Dermatology Outpatient Clinic, Faculty of Medicine, Menoufia University, and Shibin El Kom Educational Hospital. All the patients underwent were performed: Complete history taking, clinical examination, laboratory investigation to determine leptin concentration using solidphase ELISA and skin biopsies.
The serum leptin level was significantly higher in psoriatic patients than in controls. There were statistically significant correlations between the serum leptin level and PASI score and duration of the disease, but insignificant correlations with respect to other clinical and histopathological parameters.
The study supports the view that leptin may be involved in the pathogenesis of psoriasis in overweight individuals.
Keywords: leptin, psoriasis, psoriasis pathogenesis
|How to cite this article:|
Alaa H M, Seham A K, Mohamad A E, Azza G F, Mohamed F E. The role of leptin in the pathogenesis of psoriasis. Menoufia Med J 2015;28:387-91
|How to cite this URL:|
Alaa H M, Seham A K, Mohamad A E, Azza G F, Mohamed F E. The role of leptin in the pathogenesis of psoriasis. Menoufia Med J [serial online] 2015 [cited 2021 May 17];28:387-91. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/387/163890
| Introduction|| |
Psoriasis is a common inflammatory T-cell-mediated skin disorder, affecting 2-3% of the population. It is a chronic papulosquamous skin disease characterized with an overexpression of proinflammatory cytokines produced by Th1 cells and a relative underexpression of Th2 cytokines  . The etiology of psoriasis remains unknown, but the disease is believed to have an autoimmune basis and a strong genetic component. Leptin is important for cell-mediated immunity, and CD4-positive T-cells are hyperactive in leptin-deficient mice  . Leptin appears to contribute to Th1 and suppresses Th2 immune responses  . Nowadays, psoriasis is considered a systemic disease with significant cardiovascular comorbidity. Studies suggested that hyperleptinemia might play an important role in obesity-associated cardiovascular diseases, including atherosclerosis  .
| Patients and methods|| |
This study included 40 consecutive patients with plaque-type psoriasis and 10 healthy controls with no history of systemic or skin disease and with matched age, sex and BMI. The patients were recruited from the Dermatology Outpatient Clinic, Faculty of Medicine, Menoufia University, and Shibin El Kom Educational Hospital. All patients gave their formal consent. The protocol was approved by the Ethical Committe of the Faculty of Medicine, Menoufia University. Patients with psoriasis were subdivided into four groups on the basis of their psoriasis area and severity index (PASI) scores and BMI.
Group I comprised 10 patients with mild to moderate psoriasis (PASI < 15) and normal BMI.
Group II comprised 10 patients with severe psoriasis (PASI > 15) and normal BMI.
Group III comprised 10 patients with severe psoriasis (PASI > 15) and high BMI.
Group IV comprised 10 patients with mild to moderate psoriasis (PASI < 15) and high BMI.
For all patients the following procedures were performed:
Skin biopsies of 3 mm from the lesional skin of psoriatic patients. These biopsies were obtained from the active psoriatic plaques from the extensor surfaces of the extremities of the patients, as well as from healthy skin from the extensors of the controls' extremities. The samples were fixed in 10% formaldehyde and embedded in paraffin. Sections were cut and stained with H&E for the 40 patients and for 10 individuals of the control group. Each of this paraffin-preserved blocks was cut and prepared for immunohistochemical staining of the leptin tissue. Serum leptin assay (according to the kit instructions): the kit was purchased from LDN Leptin ELISA (EIA-120180) (Germany). Tissue leptin assay (according to the kit instructions): the kit was purchased from EnzoLife sciences (ALX-210-105-R050) (Germany).
- Complete history taking.
- Thorough clinical examination.
- Determination of leptin concentration using solid-phase ELISA: This was measured from 3 ml of blood taken from each patient.
The H&E-stained sections were examined under a light microscope to confirm the diagnosis of psoriasis.
Immunohistochemical staining showed leptin expression as brownish discoloration of cytoplasmic and diffuse pan-epidermal expression pattern in psoriatic skin and dermal inflammatory cells. Semiquantitative evaluation was used to determine cells showing positive expression by viewing 10 fields at ×100, ×200, and ×400 magnification. Staining intensity was graded as negative (-), mild (+), moderate (++), and strong (+++).
Statistical analysis was carried out using SAS program (North Carolina State University, USA)  . One-way analysis of variance followed by Duncan's multiple range test was used to test the effect of tissue leptin, PASI severity and PASI score on different parameters. Student's t-test (procedure means of SAS) was used to test the effect of sex, family history, treatment and PASI score on different parameters. Statistical significance was considered when P value was 0.05 or less, highly significant when P value was 0.01 or less, and nonsignificant when it was greater than 0.05.
| Results|| |
In this study, the serum leptin level was significantly higher in psoriatic patients than in controls (P < 0.001) [Table 1] and [Figure 1]. There were statistically significant correlations between the serum leptin level and PASI score and duration of the disease, but insignificant correlations with respect to other clinical and histopathological parameters [Table 2] and [Table 3].
|Table 2 Relationship between serum leptin and clinical and histopathological data|
Click here to view
|Table 3 Correlation between serum leptin and other parameters in the studied groups|
Click here to view
Biopsy from a psoriatic lesion showed regular acanthosis, parakeratosis, hyperkeratosis and elongated rete ridges. The dermis showed angiogenesis and chronic inflammatory cells. Most of our cases presented with moderate acanthosis, mild parakeratosis, mild inflammation and marked angiogenesis [Table 4] and [Figure 2].
|Figure 2: A psoriatic lesion showing regular acanthosis, hyperkeratosis and elongated rate ridges. The dermis showed angiogenesis and chronic inflammatory cells (hematoxylin and eosin, ×20 0)|
Click here to view
Epidermal leptin expression in psoriatic patients showed positive cytoplasmic immunoreactivity in epidermal keratinocytes with variable degrees of staining intensity - mild, moderate and strong. Dermal leptin expression in psoriatic patients showed positive dermal inflammatory and endothelial cells with variable degrees of staining intensity - mild moderate and strong [Figure 3].
|Figure 3: Cytoplasmic immunoreactivity for leptin in psoriatic epidermis with scattered nuclear expression. Strongly positive leptin expression is also seen in the infl ammatory and endothelial cells of the dermis (immune, ×2 00).|
Click here to view
The results of studied clinical and histopathological parameters in psoriatic subgroups showed a highly significant difference with respect to duration (P < 0.001), serum leptin (P < 0.001) and dermal leptin expression (P < 0.001), and significant difference with respect to angiogenesis (P = 0.03) and epidermal leptin expression (P = 0.02) [Table 5].
| Discussion|| |
Psoriasis, a common and enigmatic recurrent cutaneous disease, is no longer regarded as a disease of the skin only but rather as an immune-mediated chronic inflammatory disease  .
Psoriasis is associated with an overexpression of proinflammatory cytokines produced by Th1 cells and a relative underexpression of Th2 cytokines  .
Adipokines, a general term commonly used to describe bioactive products produced by adipose tissue, may serve as a missing link in the causal relationship between psoriasis and comorbidities related to obesity. Major adipokines, known to be dysregulated in obesity, such as leptin, adiponectin, resistin and visfatin, are also found to be present in abnormal levels in patients with psoriasis  .
It is noteworthy that leptin, a hormone synthesized and secreted by adipocytes, regulates body weight by inhibiting food intake and stimulating energy consumption  .
Accordingly, a strong relation seems to exist between the immunopathogenesis of psoriasis and the proliferative and immunological effects of leptin. Previous studies have suggested the role of leptin in the pathogenesis of psoriasis vulgaris , .
Hence, this study was performed to evaluate serum leptin levels in patients with psoriasis, compared with controls. In addition to immunohistochemical evaluation of tissue leptin in psoriatic and healthy control skin, we aimed to throw light on the possible hypothesized role of leptin in the etiopathogenesis of this disease entity.
In the current study, BMI values of our psoriatic patients ranged from 18 to 35, with a mean value of 26.05 ± 5.60. There was significant positive correlation between the severity of psoriasis - based on PASI score - and BMI of psoriatic cases (P = 0.02). Our result was in agreement with that of many other investigators  .
In this study, we also reported highly significant serum leptin level in psoriatic cases (27.35 ± 30.31) compared with controls (4.10 ± 1.35) (P < 0.001). This result is in line with that of many other investigators , .
In the present study, serum leptin levels recorded its highest values among obese patients with severe psoriasis (group III) (64.91 + 35.8), that was significantly higher than those of nonobese patients or those with mild to moderate psoriasis (P < 0.001). Moreover, we reported a significant positive correlation between serum levels of leptin and BMI in our psoriatic cases (r = 0.039, P = 0.03). In agreement with our result is that of Xue et al.  .
In the current study, leptin expression was assessed by immunohistochemistry in skin biopsy samples of active psoriatic plaques and healthy controls. The results of semiquantitative evaluation revealed that leptin displayed a strong cytoplasmic and diffuse pan-epidermal expression pattern in psoriatic skin. In addition, dermal inflammatory cells were strongly positive. In healthy skin, we observed moderate leptin immunoreactivity limited to the basal keratinocytes in the epidermis, to endothelial cells, fibroblasts and to eccrine gland cells. The levels of epidermal and dermal tissue leptin expression were significantly higher in psoriatic cases compared with healthy skin (P = 0.02 and 0.005, respectively). Moreover, epidermal and dermal tissue leptin expression was (100%) strong in obese psoriatic cases with severe form of psoriasis (group III), and significantly higher than those of nonobese patients or those with mild to moderate psoriasis (P = 0.02 and P < 0.001, respectively). In addition, we reported a significant positive association between dermal leptin levels and severity of psoriasis based on PASI score, disease duration, positive family history and serum leptin level (P = 0.001), and also a positive association between dermal leptin levels and parakeratosis (P = 0.001) and angiogenesis (P < 0.01) in patients with psoriasis.
Accordingly, it seems that the immunological role of leptin and the immunopathogenesis of psoriasis may overlap. It was found that high concentrations of leptin in psoriatic tissue may induce local production of amphiregulin, an endothelial growth factor, which together with leptin and resistin stimulates the production of chemokine (CXCL8) in cultured psoriatic cells. This was suggested to drive the keratinocyte proliferation that is characteristic for psoriasis  .
As the contribution of tissue dermal leptin expression to family history, serum leptin level, parakeratosis, and angiogenesis in patients with psoriasis has not been addressed, we cannot compare our results with former studies.
| Conclusion|| |
The current study revealed that the greater the severity of psoriasis (higher the PASI score), the greater the rise in the serum leptin levels and higher the severity of the tissue leptin.
Our study supports the view that leptin may be involved in the pathogenesis of psoriasis in overweight individuals.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Naldi L, Chatenoud L, Linder D, Belloni F, et al.
Cigarette smoking, body index and stressful life events as risk factors for psoriasis: results from an Italian case-control study. J Invest Dermatol 2005; 124
Frank S, Stallmeyer B, Kämpfer H, Kolb N, et al.
Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest 2000; 106
Johnston A, Arnadottir S, Gudjonsson JE, Aphale A, et al.
Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation. Br J Dermatol 2008; 159
Kremers HM, McEvoy MT, Dann FJ, Gabriel SE. Heart disease in psoriasis. J Am Acad Dermatol 2007; 57
SAS. STAT/user's guide
. 3rd ed. Cary, NC, USA: SAS Institute; 1988. 37-112.
Schon MP, Boehncke WH, Psoriasis. N Engl J Med 2005; 352
Gudjonsson JE, Karason A, Antonsdottir AA. HLA-Cw6-positive and HLA-Cw6-negative patients with psoriasis vulgaris have distinct clinical features. J Invest Dermatol 2002; 118
Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002; 26
Muoio D, Dohm G. Lynis, peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002; 16
Cerman AA, Bozkurt S, Sav A,Tulunay A, et al.
Serum leptin levels, skin leptin and leptin receptor expression in psoriasis. Br J Dermatol 2008; 159
Wang Y, Chen J, Zhao Y, Geng L, et al.
Psoriasis is associated with increased levels of serum leptin. Br J Dermatol 2008; 158
Zhang N, Pan HF, Ye DQ. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem 2011; 353
Aly DG, Abdallah IY, Elsaie ML. Eevated serum leptin levels in nonobese patients with psoriasis. J Drugs Dermatol 2013; 12
K Xue, H Liu, Q Jian, B Liu, et al.
Leptin induces secretion of pro-inflammatory cytokines by human keratinocytes in vitro - a possible reason for increased severity of psoriasis in patients with a high body mass index. Exp Dermatol 2013; 22
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|This article has been cited by|
||Adverse childhood experiences and tramadol use in Nigeria: the mediating role of sociosexuality in a predominantly male student sample
| ||Desmond Uchechukwu Onu,Chuka Mike Ifeagwazi,Charles Tochukwu Orjiakor,Steven Kator Iorfa |
| ||Journal of Substance Use. 2020; : 1 |
|[Pubmed] | [DOI]|
||“With tramadol, I ride like a Jaguar”: a qualitative study of motivations for non-medical purpose tramadol use among commercial vehicle operators in Kumasi, Ghana
| ||Prince Peprah,Williams Agyemang-Duah,Emmanuel Appiah-Brempong,Adjei Gyimah Akwasi,Anthony Kwame Morgan |
| ||Substance Abuse Treatment, Prevention, and Policy. 2020; 15(1) |
|[Pubmed] | [DOI]|