The effect of secukinumab treatment for psoriasis on serum cytokines and correlation with disease severity

Abstract Objective To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients’ serum Methods Enzyme‐linked immunosorbent assay was used to detect interleukin (IL)‐1β and IL‐1RA associated with intrinsic immunity; IL‐6, IL‐18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL‐12, tumour necrosis factor (TNF)‐α, and interferon (IFN)‐γ associated with Th1; IL‐23, IL‐17A, and IL‐22 associated with Th17; Thymus activation regulated chemokine (TARC), IL‐13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)‐A and IL‐10 associated with angiogenesis; and IFN‐γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL‐23, IL‐17A, IL‐22 associated with Th17; TARC, IL‐13, DEFB2 associated with Th2; VEGF‐A, IL‐10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severity［Psoriasis Area Severity Index(PASI) score］, age, and disease duration were analyzed. Results The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL‐6; IL‐18, GROα, IFN‐γ, TNF‐α, VEGF‐A, and IL‐17A were significantly higher than normal. And IL‐17A and IFN‐γ were positively correlated with disease duration and age, and IL‐18 was positively correlated with PASI score. The expression levels of IL‐6, GROα, VEGF‐A, IFN‐γ, TNF‐α, IL‐17A and IL‐23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN‐γ, VEGF‐A, TARC, IL‐13, and DEFB2 were still significantly higher than those of normal subjects after treatment Conclusions secukinumab clears skin lesions by antagonizing IL‐17A and simultaneously decreasing the expression levels of IL‐6, GRO α, VEGF‐A, IFN‐γ, TNF‐α, IL‐17A, and IL‐23.


INTRODUCTION
Psoriasis is a chronic, relapsing inflammatory disease. It mainly affects the skin and joints and can be combined with co-morbidities such as Psoriasis can present with eczema-like changes, and it is uncertain whether Th2-associated TARC, DEFB2, and IL-13 are also involved in the pathogenesis of psoriasis. In this study, we analyzed the changes of 17 cytokines in serum before and after treatment in 12 patients with moderate-to-severe psoriasis treated with secukinumab to assess the relationship between these cytokines and psoriasis severity andtreatment, and to investigate the possible mechanisms for the treatment of psoriasis with secukinumab.

Differences in the expression of different cytokines in serum of patients with moderate to severe psoriasis
Serum expression of IL-6, IL-18, GROα associated with intrinsic immunity and neutrophils; IFN-γ, TNF-α associated with Th1; VEGF-A associated with angiogenesis; IL-17A associated with Th17; TARC, DEFB2, IL-13 associated with Th2 were significantly higher than normal in patients with moderate to severe psoriasis (p < 0.05). The expression levels of IL-12, IL-23, PCT, and IL-1β were greater than those of normal subjects before treatment, but not statistically significant. The expression levels of serum IL-22, IL-1RA, and IL-10 in patients with moderate to severe psoriasis were lower than normal, and the decreased level of IL-22 was significantly different compared with normal subjects (p < 0.01) ( Table 1, Figures 1-6).

Comparison of serum cytokine levels in psoriasis patients with normal subjects after secukinumab treatment
Serum angiogenesis-related VEGF-A; Th1-related IFN-γ and Th2related DEFB2 serum expression levels remained significantly higher in patients with moderate-to-severe psoriasis after secukinumab treatment than in normal subjects. the expression levels of VEGF-A and IFN-γ were significantly lower after secukinumab treatment than before treatment (

Correlation of different cytokine expression levels with disease duration and disease severity
Both IL-17A and TNF-α were positively correlated with disease duration and age; IL-18 was positively correlated with PASI; and TARC was correlated with gender, with males significantly higher than females.

F I G U R E 1
Expression levels of IL-1ra, IL-1β, L-6 cytokines in serum of psoriasis patients before and after treatment and in normal subjects.

DISCUSSION
Psoriasis is a common chronic inflammatory disease characterized by The results of this study showed that IFN-γ and VEGF-A expression levels were significantly higher than normal in psoriasis patients before treatment and decreased significantly after secukinumab treatment, but the levels remained significantly higher than normal after treatment. IFN-γ is the only member of the type II interferon family.
In psoriasis Th1 cells are a potential source of IFN-γ. Previously, the Th1 pathway was considered to be the main pathogenic pathway in psoriasis. 1  antagonists.

Reagents and equipments
ELIASA kit is from Wuhan Elabscience; Enzyme microplate analyzer (Bethen, USA).  Table 1 for details). Fifteen cases of healthy individuals matched for sex and age were also selected as controls, and the general information of the two groups was significantly different, as shown in Table 1.

Methods
The cytokines in the serum were detected by enzyme-linked immunosorbent assay (ELISA), which was operated strictly according F I G U R E 7 Correlation of different cytokine expression levels with disease duration and disease severity.

F I G U R E 7 Continued
to the instructions of ELISA kit, and finally the OD value of each well was measured at 450-nm wavelength of the enzyme calibrator, and the concentration of each cytokine in the serum was calculated according to the standard curve.

Statistical analysis
All data were analyzed using the Statistical Package for Social Sciences (SPSS) 26 program on the computer. All data are given as mean ± standard deviation. Wilcoxon signed rank test was used for pretreatment and posttreatment, Mann-Whitney U test for patients and healthy controls, and Spearman rank correlation test was used to assess correlations. p-Value < 0.05 was considered statistically significant.