The knowledge about the role of cytokines in psoriasis has developed in the last several years. Initially, only Th1 cells and cytokines secreted by these cells, like TNF-
In the 1990s, Th17 cells were described as a new T-cell population that produces IL-17, IL-6, IL-21, IL-22, and TNF [
Th22 cells have been recently described as inflammatory CD4+ T cells that produce cytokines such as IL-22, IL-26, and IL-13 of which IL-22 is the most important functional cytokine. Th22 cells do not express IL-17A or IFN-
IL-20 resembles IL-22 structurally and belongs to the same cytokine family. IL-22 can stimulate IL-20 production in keratinocytes [
The differentiation of main three T cell subsets involved in the pathogenesis of psoriasis, as well as Th1, Th17, and Th22 cytokine production are illustrated in Figure
Th1, Th17, and Th22 cytokines in the pathogenesis of psoriasis.
The aim of the study was to assess the serum levels of some cytokines involved in the Th17 and Th22 responses in psoriatic patients.
The study comprised 60 psoriatic patients, 50 males (83.33%) and 10 females (16.67%), as well as 30 healthy controls. The studied patients’ age was between 18 and 69 years,
The skin lesions severity was assessed with the use of Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA) scores. The PASI value in the studied group was from 4.8 to 64.2 and
Blood samples were collected from psoriatic patients and controls and were centrifuged for 15 minutes at 1000 ×g. Then, serum samples were subdivided into small aliquots to be stored at −80°C until tested for cytokine levels. ELISA kits were used to determine IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 (R&D Systems, Minneapolis, MN, USA) serum levels, according to the manufacturer’s instructions.
Statistical analyses were performed using STATISTICA software. Continuous variables were presented as mean ± standard deviation, while categorical variables were presented as absolute and relative frequencies. Mann-Whitney’s
The statistical analyses of the conducted study results revealed significantly higher serum levels of IL-6, IL-20, and IL-23 in psoriatic patients comparing to healthy controls (Table
The selected cytokine serum concentrations in the psoriatic patients and the control group.
Cytokine | Psoriasis | Control | |
---|---|---|---|
IL-6 (pg/mL) | <0.001 | ||
IL-12 (pg/mL) | 0.075 | ||
IL-17 (pg/mL) | 0.684 | ||
IL-20 (pg/mL) | <0.001 | ||
IL-22 (pg/mL) | <0.001 | ||
IL-23 (pg/mL) | 0.094 |
Comparing of selected cytokine serum concentrations in the psoriatic patients and the control group.
Significantly higher IL-6 values were found in the psoriatic patients in comparison to the control group (
IL-6 contributes to the Th17 cell line’s involvement in numerous processes of inflammation and autoimmunity by preventing the proliferation of T regulatory cells [
Elevated serum IL-6 was observed in psoriatic patients in many studies [
Significantly higher IL-20 values were found in the psoriatic patients in comparison to the control group (
IL-20 is produced by keratinocytes in the presence of IL-22, TNF-
There are not many studies concerning IL-20 serum level, but increased levels of IL-20 were noted in lesional skin as well as in the blood in psoriatic patients [
A significantly higher increase in IL-22 was observed in psoriatic patients in comparison with the healthy controls (
IL-22 is a member of the IL-10 cytokines family and is mainly produced by Th17, Th22, and mucosal NK cells [
In psoriasis, IL-22 is overexpressed most probably as a result of upregulated IL-23 and IL-6 levels [
No significant differences were found in the IL-12 and IL-23 concentrations between the psoriatic patients and control group (
IL-23 together with IL-12 belongs to the IL-12 family and are both structurally related; IL-12 is formed by the p40 and p35 subunits; IL-23 consists of p40 and p19 subunits [
Although both IL-12 and IL-23 are present in psoriasis, studies support that IL-23, rather than IL-12, is crucial during the pathogenesis of psoriasis. IL-23 is overexpressed in psoriasis lesional skin, as shown for example, by increased p40 and p19 mRNA levels but not always p35 [
IL-23 has the influence on sustenance and amplification of the chronic inflammation in psoriasis [
No significant differences were found in the serum IL-17 concentrations between the psoriatic patients and control group (
IL-17 (IL-17A) is a member of a newly identified cytokine family comprising IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (IL-25), and IL-17F. IL-17 and IL-17F have a proinflammatory activity inducing the expression of proinflammatory cytokines, colony-stimulating factors, and chemokines from dendritic cells, neutrophils, T cells, monocyte/macrophages, and epithelial cells [
IL-17 is undetectable in normal skin, and biological therapy that inhibits Th17 pathways results in reduced expression of IL-17 and IL-23 and improved disease outcomes [
In addition, an analysis of mutual correlations between the concentrations of selected cytokines in the psoriatic patients was conducted. A significant positive correlation between the IL-23 and IL-17 values was found (
We believe that the results of our study confirm involvement of Th17 and Th22 cytokines in psoriasis pathogenesis. Elevated IL-22 level without increase of IL-17 level may suggest that Th22 role is more significant in the inflammatory process of psoriasis. Very high concentrations of IL-22 in the patients’ serum can be connected with intensive IL-6 stimulation. IL-22 and IL-20 itself induce production of IL-20, which is elevated in our study. It seems that IL-6, which initiates Th17 and Th22 pathways in psoriasis, may be helpful in the clinical practice as a soluble biomarker of the disease activity and its prognosis. The development of new therapeutical strategies targeting the initial step of cytokine network activation, for example, IL-6, may reduce the next events of inflammatory reactions and prevent the psoriasis exacerbation and systemic complications. Furthermore, serum levels of IL-20, IL-22, and IL-17, which correlated with the clinical severity and activity of psoriasis, may be objective parameters of successful treatment and may be used in the followup.
Body Surface Area
Enzyme-linked immunosorbent assay
Human beta-defensin
Interferon
Interleukin
Matrix metalloproteinase
Messenger ribonucleic acid
Natural killer
Psoriasis Area and Severity Index
Physician Global Assessment
Transforming growth factor
T helper
Tumor necrosis factor.
This work was supported by a Grant DS164.