|Year : 2016 | Volume
| Issue : 4 | Page : 818-825
Study of interleukin-22 in patients with psoriasis in Menoufia University Hospitals
Ghada R El-Hendawy1, Ahmed A Salama1, Mohamed A Gaber2, Eman Mhros MBBCH 1
1 Department of Microbiology and Immunology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Dermatology and Venereology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||08-Mar-2015|
|Date of Acceptance||17-May-2015|
|Date of Web Publication||21-Mar-2017|
Shebin El Kom City, Menoufia Governorate, 32511
Source of Support: None, Conflict of Interest: None
The aim of this study was to detect a relation between serum levels of interleukin-22 (IL-22) in patients with psoriasis and also to detect a relation of IL-22 with psoriasis area and severity index (PASI).
IL-22 is highly expressed in several different chronic inflammatory conditions, including psoriasis, inflammatory bowel disease, and rheumatoid arthritis. The best studied function for IL-22 is within the skin, as it has an inflammatory role during skin inflammation.
Materials and methods
The study was conducted on 40 patients with psoriasis and 20 age-matched and sex-matched healthy individuals. All patients were subjected to history taking and complete medical examination. Serum levels of IL-22 were measured by enzyme-linked immunosorbent assay technique. Serum levels of IL-22 were statistically analyzed in relation to PASI.
The serum levels of IL-22 were highly elevated in patients with psoriasis compared with healthy people (P < 0.001). The serum IL-22 was significantly higher in patients with severe psoriasis as compared with those with mild and moderate psoriasis. The serum levels of IL-22 were significantly higher in patients with psoriasis experiencing itching as compared with those not experiencing itching (P < 0.001). There was no statistically significant difference between the serum levels of IL-22 and smoking.
The significant elevation in the serum level of IL-22 in patients with psoriasis when compared with that of healthy controls and the significant elevation in the serum levels of IL-22 with advanced PASI score are suggestive of IL-22 playing a fundamental role in pathogenesis of psoriasis.
Keywords: interleukin-22, psoriasis, psoriasis area and severity index
|How to cite this article:|
El-Hendawy GR, Salama AA, Gaber MA, Mhros E. Study of interleukin-22 in patients with psoriasis in Menoufia University Hospitals. Menoufia Med J 2016;29:818-25
|How to cite this URL:|
El-Hendawy GR, Salama AA, Gaber MA, Mhros E. Study of interleukin-22 in patients with psoriasis in Menoufia University Hospitals. Menoufia Med J [serial online] 2016 [cited 2022 Aug 15];29:818-25. Available from: http://www.mmj.eg.net/text.asp?2016/29/4/818/202485
| Introduction|| |
Psoriasis is a chronic inflammatory cell-mediated disease affecting skin and usually presenting with symmetric, well-demarcated, erythematous plaques with overlying silvery scales, often with accompanying pruritus . It has been proposed that various cytokines from infiltrating leukocytes orchestrate the development of psoriasis. What molecular links mediate the cross-talks between the infiltration of leukocytes and the abnormalities of keratinocytes in psoriatic skin is one of the important questions underlying the pathogenesis of psoriasis. Progress in the past several years has identified interleukin-22 (IL-22) as one of the key mediators that regulate many of the important pathogenic features of epidermis in psoriatic skin .
IL-22 was identified in 2000 by Belgian investigators searching for genes induced by IL-9 in murine T cells and identified a gene encoding a novel protein which seemed to be structurally related to the class II cytokine IL-10. This protein was initially named IL-10-related T-cell-derived inducible factor. Shortly following its discovery, IL-10-related T-cell-derived inducible factor was shown to be present in T cells, mast cells, thymus, and brain and to activate signal transducer and activator of transcription-3 (STAT-3) .
IL-22 has been identified in a variety of tissues and cell types and has been shown to play a role in a wide range of human diseases. IL-22 appears to act predominantly on IL-22 receptor-1 (IL-22-R1)-positive epithelial and endothelial cells. In some settings, IL-22 appears to protect against damage due to inflammation, whereas in other settings, it seems to contribute to the development and persistence of disease .
The expression of IL-22 from leukocytes in psoriatic skin is directly regulated by IL-23, whose indispensable role in psoriasis has been proven by clinical data with therapeutics blocking IL-23 pathway and by genome-wide genetic association data . IL-22 induces hyperplasia, abnormal differentiation, and the expression of many psoriatic marker genes such as psoriasin (S100A7) from keratinocytes . Elevated expression of IL-22 mRNA has been found in lesional skin. Consistently, there is also increased IL-22 protein detected in the serum samples from patients with psoriasis .
Keratinocytes are the major downstream targets of IL-22 in the skin . Many of the downstream phenotypes induced by IL-22 from keratinocytes are also observed in epidermal keratinocytes from lesional psoriatic skin. For example, in cultured reconstituted human epidermis (RHE), IL-22 induces prolonged STAT-3 activation, which is readily detectable in involved psoriatic epidermis . In vitro, IL-22 treatment results in pronounced proliferation and altered differentiation process of the cultured epidermal keratinocytes, resembling acanthosis of psoriatic skin .
Normal epidermis contains four major keratinocyte layers: basal layer, spinous layer, granular layer, and cornified layer . In cultured epidermis, IL-22 enhances the proliferative capacity of epidermal keratinocytes, leading to increase in overall thickness of the RHE .
In addition to these cellular changes, IL-22 induces the expression of many genes that are involved in innate host defense, inflammatory response, wound healing, re-epithelialization, and differentiation from RHE, for example, IL-22 regulates the expression of many antimicrobial peptides such as S100 family proteins (e.g., S100A7 and S100A8) and β-defensin family proteins .
| Materials and Methods|| |
Study population and selection of patients
This study was conducted at the Microbiology and Immunology Department, Faculty of Medicine, Menoufia University in collaboration with Dermatology and Venereology Department, Faculty of Medicine, Menoufia University during the period from November 2013 to October 2014.
It involved two groups: group I included 40 patients with psoriasis (23 males and 17 females) and group II included 20 age-matched and sex-matched healthy individuals.
Inclusion criteria were as follows: patients older than 15 years who presented with chronic plaque psoriasis and had not received any systemic or topical treatment for 1 month before the study.
Exclusion criteria were as follows: patients with psychological problems, as they could influence the study; those with other skin conditions precluding proper assessment of psoriasis severity, those with associated cutaneous congenital anomalies, those with associated severe soft tissue infection, those with liver disease, those with rheumatoid arthritis, and those with chronic inflammatory bowel disease. Informed consent was taken from both the patient and control groups before the beginning of the study.
After signing an informed consent form, patients were subjected to the following:
- History taking: personal history, detailed history of psoriasis regarding onset and duration of the disease, family history of psoriasis, and comorbid conditions
- Clinical examination: general examination and investigation of cutaneous lesions were performed, and classification of psoriasis severity according to psoriasis area and severity index (PASI) was done as follows:
Psoriasis area and severity index score
It is the most widely used tool to assess psoriasis disease severity in clinical trials.
The principles of psoriasis area and severity index score calculation
The body is divided into four sections: head (H) (10% of a person's skin), upper extremities (U) (20%), trunk (T) (30%) and lower extremities (L) (40%). Each of these areas is scored by itself, and then the four scores are combined into the final PASI. For each section, the percent of area of skin involved is estimated and then transformed into grades from 0 to 6:
- 0% of involved area, grade 0;
- <10% of involved area, grade 1;
- 10–29% of involved area, grade 2;
- 30–49% of involved area, grade 3;
- 50–69% of involved area, grade 4;
- 70–89% of involved area, grade 5;
- 90–100% of involved area, grade 6.
Within each area, the severity is estimated by three clinical signs: erythema (redness), induration (thickness), and desquamation (scaling). Severity parameters are measured on a scale of 0 to 4, from none to maximum. The sum of all three severity parameters is then calculated for each section of the skin, multiplied by the area score for that area and multiplied by weight of respective sections (0.1 for head, 0.2 for arms, 0.3 for body, and 0.4 for legs).
PASI = 0.1 (Rh + Th + Sh) Ah + 0.2 (Ru + Tu + Su) Au + 0.3 (Rt + Tt + St) At + 0.4 (Rl + Tl + Sl) Al.
PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). Patients were classified according to Louden et al.  and Kimball et al.  by their PASI score as follows:
- Mild psoriasis: PASI <7
- Moderate psoriasis: PASI 7–12
- Severe psoriasis: PASI >12.
Venous blood samples (5 ml) were taken under sterile conditions in serum separator tubes from patients and controls. After clot formation, samples were centrifuged at 1000g for 15 min.
Sample preparation and storage
Samples were stored to be assayed within 24 h at 2–8°C. For long-term storage, aliquoted and freezed samples were stored at −20°C. Repeated freeze-thaw cycles were avoided.
Quantification of interleukin-22 serum levels
Serum IL-22 levels were quantified by using Boster's human IL-22 enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions (Boster Biological Technology Co Ltd, Fremont, California, USA). Boster's human IL-22 ELISA kit was based on standard sandwich ELISA technology .
The data collected were tabulated and analyzed by (SPSS, version 20; SPSS Inc., Chicago, Illinois, USA) version 20 on IBM compatible computer.
The results were expressed by applying ranges, mean ± SD, c2-test, Mann–Whitney test, t-test, Kruskal–Wallis test, and P values. P value less than 0.05 was considered to be significant.
Pearson correlation was used for normally distributed quantitative variables, whereas Spearman correlation was used for quantitative variables that were not normally distributed or when one of the variables is qualitative.
| Results|| |
The patients group included 40 patients with psoriasis, with 17 females (42.5%) and 23 males (57.5%). Their ages ranged from 15 to 77 years with a mean of 39.70 ± 16.68. There were nine smokers (22.5%) and 31 nonsmokers (77.5%). The control group included 20 normal individuals, with 11 females (55.0%) and nine males (45.0%). Their ages ranged from 18 to 69 years, with a mean of 33.50 ± 14.94. There were seven smokers (35%) and 13 nonsmokers (65%). There were no statistically significant differences between the two studied groups regarding age, sex, and smoking.
There were 55% of patients who experienced itching, whereas 45% did not experienced itching. There were 45% with mild psoriasis, 32.5% with moderate psoriasis, and 22.5% with severe psoriasis. There were 55% of patients with generalized psoriasis and 45% of patients with localized psoriasis.
The mean value of IL-22 serum level in patients with psoriasis was 875.77 pg/ml, whereas in controls, it was 7.13 pg/ml. The mean serum level of IL-22 in patients experiencing itching was 969.07 pg/ml, whereas in patients not experiencing itching was 799.43. The mean serum level of IL-22 in patients with mild psoriasis was 793.66 pg/ml, in patients with moderate psoriasis was 932.52 pg/ml, and in patients with severe psoriasis was 957.99 pg/ml. There was no statistically significant correlation in the serum level of IL-22 and duration of the disease (P = 0.33).
The serum level of IL-22 ranged from 693.86 to 1055.66 pg/ml in the patients group, with a mean of 875.77 ± 107.10 pg/ml. The serum level of IL-22 in control group ranged from 3.19 to 18.59 pg/ml, with a mean of 7.13 ± 5.56. There was a highly increase in the serum level of IL-22 in cases as compared with controls.
The serum levels of IL-22 in smoking patients ranged from 709.60 to 1026.90 pg/ml, with a mean of 844.16 ± 100.83 pg/ml, whereas the serum levels of IL-22 in nonsmoking patients ranged from 963.86 to 1055.66 pg/ml, with a mean of 884.94 ± 108.69 pg/ml. There was no statistically significant difference in the serum levels of IL-22 between smokers and nonsmokers.
The serum levels of IL-22 in patients with psoriasis experiencing itching ranged from 891.00 to 1055.66 pg/ml, with a mean value of 969.07 ± 60.27 pg/ml. The serum levels of IL-22 in patients without itching ranged from 693.86 to 946.26 pg/ml, with a mean value of 799.43 ± 69.25 pg/ml. The serum levels of IL-22 were significantly higher in patients with psoriasis experiencing itching as compared with those not experiencing itching (P < 0.001).
There were 18 patients with psoriasis who complained of itching: one patient with mild psoriasis (5.6%), nine patients with moderate psoriasis (50%), and eight patients with severe psoriasis (44.4%). There were 22 patients with psoriasis not complaining of itching: 17 patients with mild psoriasis (77.3%), four patients with moderate psoriasis (18.2%), and one patient with severe psoriasis (4.5%). Itching is increased in patients with severe psoriasis than in those with mild psoriasis. There was a high statistically significant correlation between presence of itching and severity of psoriasis (P < 0.001).
Regarding severity, patients with psoriasis were classified into three groups: mild, moderate, and severe. The serum levels of IL-22 in mild group ranged from 693.86 to 946.26 pg/ml, with a mean value of 793.66 ± 71.06 pg/ml; in moderate group from 829.46 to 1045.02 pg/ml, with a mean value of 932.52 ± 77.48 pg/ml; and in severe group from 751.10 to 1055.66 pg/ml, with a mean value of 957.99 ± 96.42 pg/ml. The serum level of IL-22 was significantly higher in patients with severe psoriasis as compared with those with mild and moderate psoriasis. There was a high statistically significant difference in the serum levels of IL-22 and PASI, with P value less than 0.001.
| Discussion|| |
This study was performed at Menoufia University Hospitals to determine the serum levels of IL-22 in patients with psoriasis and to correlate those levels with PASI score. The present study included 60 subjects divided into two groups: 40 patients with psoriasis and 20 healthy controls. All patients and controls were clinically evaluated, and blood samples were collected for detection of serum IL-22 by the ELISA technique. In the patient group, 23 were males (57.5%) and 17 were females (42.5%), with a mean age of 39.70 ± 16.68 years, whereas in the control group, nine were males (45%) and 11 were females (55%), with a mean age of 33.50 ± 14.94 years, with no significant differences between the patient and the control groups regarding both age and sex.
In the present study, serum levels of IL-22 in patients with psoriasis were significantly higher, with a mean value of 875.77 ± 107.10 pg/ml compared with controls. That result was in agreement with the study done byFujita , Choe et al. , Meephansan et al. , Nakajima et al. , Lo et al. , and Boniface et al. , who found higher serum levels of IL-22 in patients with psoriasis than in healthy controls. A finding that goes with that obtained by Coimbra et al. , who studied IL-22, IL-17, IL-23, IL-8, vascular endothelial growth factor, and tumor necrosis factor-α levels in patients with psoriasis before, during, and after psoralen-ultraviolet A and narrow band ultraviolet B therapy; they concluded that before the initiation of treatment, serum level of IL-22 was significantly higher in patients group than in control group.
Moreover, Caproni et al. studied the effect of etanercept and acitretin on serum level of IL-22 in 60 patients with psoriasis and 10 healthy controls and found that before the initiation of any treatment, serum concentration of IL-22 in patients with psoriasis was significantly higher compared with that in healthy controls.
In the present study, there was no statistically significant correlation between serum level of IL-22 and duration of psoriasis (P = 0.33), which was similar to the results obtained byAlmakhzangy et al. .
The present study shows that there was a statistically significant correlation between serum level of IL-22 and PASI (P < 0.001). A result that is in agreement with findings reported by Nakajima et al. , who studied the kinetics of circulating T-helper cytokines (IL-22, IL-17, and IL-23) in patients with psoriasis and reported that IL-22 values were positively correlated with PASI score; these results suggested that serum IL-22 is a good marker for the clinical severity of psoriasis. No detectable serum levels of IL-17 or IL-23 were found in both groups. There are possibilities that such cytokines might be involved in the very early phase of psoriasis development or might be present only in the lesional skin.
This was also reported by Almakhzangy et al. , who studied the serum levels of IL-22 and IL-17 in patients with psoriasis and found that the means of serum levels of IL-17 and IL-22 in patients with psoriasis were significantly correlated with the disease severity measured by PASI. Also, Lo et al. , who studied correlation between serum IL-22, IL-17, and IL-6 and PASI, found that Pearson correlation test revealed that serum IL-22 concentration, but not IL-17, in patients with psoriasis correlated well with PASI, indicating that the serum IL-22 is a good marker of clinical severity of psoriasis.
In agreement with the present study, Meephansan et al. , who studied the effect of methotrexate on serum level of IL-22, reported that before the initiation of treatment, IL-22 was significantly higher in patients with severe psoriasis (PASI > 15) compared with those with moderate psoriasis (PASI = 10–15), with P value of 0.001*.
On the contrary, Caproni et al.  studied the effect of etanercept and acitretin on IL-22 and IL-17 in 60 patients with moderate and severe psoriasis and found that their mean PASI score was 21.5 ± 9. They found that before the initiation of treatment, no statistical significant correlation was found between serum IL-22 and PASI.
A nearly similar result was found byChoe et al. , who studied the comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis. They divided the patients into two groups according to clinical phenotype: chronic stable (CS) and eruptive inflammatory (EI). In their study, they measured 10 inflammatory cytokines, IL-22 was one of them, and found that in the CS group, which is characterized by large CS plaques, serum IL-22 levels were well correlated with PASI. However, interestingly, in the EI group, which is characterized by highly inflammatory, fast-spreading guttate plaques, there was no evidence of a positive correlation between serum IL-22 and PASI. They speculated that PASI might not be suitable for determining psoriasis severity in the EI stage. This might be because it is not easy to assess the extent of involvement in patients with numerous small plaques.
In the present study, there were 18 patients with psoriasis experiencing itching, and the serum level of IL-22 was significantly higher in those experiencing itching as compared with those not experiencing itching. There was a statistical significant correlation between serum level of IL-22 and the presence of itching in patients with psoriasis (P < 0.001). These results are in agreement with those reported byPark et al. , who studied the expression of cytokines in the skin and percentages of Th17 cells in the blood of patients with prurigo and psoriasis. Their study was carried out on patients with papulonodular prurigo, patients with plaque psoriasis, and healthy volunteers as control group. They found that IL-17 and IL-22 were highly expressed in patients having prurigo and psoriasis lesions, compared with those with normal skin. Moreover, the frequencies of Th17 cells were significantly higher in patients with prurigo as well as in those with psoriasis than in normal control.
In the present study, there were nine smokers (22.5%) and 31 nonsmokers (77.5%). There was no statistically significant correlation between smoking and serum levels of IL-22 (P = 0.32).
In disagreement with our study, Torii et al.  studied the tobacco smoke and its relation to Th17 generation with clinical implication to patients with psoriasis. They found that tobacco smoking increased IL-17 and IL-22 expression. These findings demonstrated the relation between tobacco smoke and IL-17 and IL-22, which exacerbate psoriasis. This difference can be explained by the larger size of the studied samples [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6] and [Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7]).
|Table 1 Sociodemographic characteristics and smoking habit among the studied groups of cases and controls|
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|Table 2 Comparison between studied groups of cases and controls regarding interleukin-22|
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|Table 3 Relationship between interleukin-22 and duration of the disease among the studied group of cases|
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|Table 4 Relationship between interleukin-22 and smoking habit among the studied group of cases|
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|Table 5 Relationship between interleukin-22 and itching among the studied group of cases|
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|Table 6 Relationship between severity of psoriasis among the studied group of cases and itching|
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|Table 7 Comparison between severity of psoriasis (psoriasis area and severity index) groups and control group regarding interleukin-22 (pg/ml)|
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|Figure 2: Severity of the disease among the studied group of patients with psoriasis.|
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|Figure 3: Type of psoriasis among the studied group of patients with psoriasis.|
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|Figure 6: Interleukin-22 among the studied cases according to severity of psoriasis.|
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| Conclusion|| |
From this study, we can conclude that patients with psoriasis have significant elevation in serum levels of IL-22 when compared with healthy people, and the severity of the disease is directly associated with higher serum levels of IL-22. Elevated serum levels of IL-22 are directly correlated with presence of itching in patients with psoriasis. On the contrary, duration of psoriasis does not affect the serum levels of IL-22.
The significant elevation in the serum levels of IL-22 in patients with psoriatic when compared with that of the healthy controls and the significant elevation in the serum levels of IL-22 with advanced PASI score suggest that IL-22 plays a fundamental role in pathogenesis of psoriasis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]