Predictive Role of IL-2R and IL-10 in the Anti-inflammatory Response and Antiplatelet Therapy of Kawasaki Disease: A Retrospective Study

Abstract

To date, Kawasaki disease (KD) has only been able to be diagnosed and evaluated using clinical characteristics. Additionally, the therapeutic effect and cardiovascular complications could not be verified until its occurrence. The present retrospective study analyzed the dynamic alterations of inflammatory cytokines, platelet (PLT) count, and subgroups of lymphocytes, such as cluster of differentiation (CD) 8+ T cells and CD19+ B cells, under different conditions in 64 children with KD. The percentage distribution of lymphocyte subgroups and the altered neutrophil lymphocyte ratio demonstrated that the inflammatory response was dominated by the B cell-mediated humoral immune response before intravenous immunoglobulin (IVIG) treatment, but mainly by T cells via cellular cytotoxic effects after IVIG treatment. Among the different types of inflammatory cytokines, the results of the present study revealed that the altered levels of interleukin-2 receptor (IL-2R) and interleukin-10 (IL-10) were closely associated with the percentage of CD8+ T cells and CD19+ B cells. Additionally, the two cytokines exhibited more sensitive fluctuations based on the status of the children with KD in various circumstances compared with other indexes, such as the percentages of CD8+ T cells and CD19+ B cells or the PLT count. These results suggested that children with KD who are ≥4 years old may benefit from IVIG but will not benefit from decreased platelet activation or suffer less cardiovascular complications. Additionally, starting clopidogrel usage earlier as an antiplatelet strategy should be considered based on the observed continuous rise in the PLT count in children with KD receiving IVIG. In conclusion, dynamically monitoring the levels of IL-2R and IL-10 has the potential to provide indications of the intensity and development of the inflammatory response in children with KD and may contribute to the early prediction and adjustment of pathological and pharmacological effects of therapy.

Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort

“…The present study revealed that during the initial phase of KD and before the first administration of IVIG, a significant decrease in the percentage of CD3 + , CD4 + and CD8 + T cells and an increase in the percentage of CD19 + B cells were observed in patients from IVIG retreatment group compared with those in the single‐dose IVIG group. These results are consistent with those of recent reports from other research groups in Shanghai 11,28,46 . Changes in the distribution of lymphocyte subsets during the acute phase of KD before treatment indicated that patients who underwent IVIG retreatment exhibited higher humoral immunity activity, stronger suppression of cellular immunity and more severe inflammatory responses than patients with single‐dose IVIG.…”

“…The level of IL‐2R is not only associated closely with alterations in the counts of CD8 + T cells and CD19 + B cells but also fluctuates rapidly along with the intensity of inflammation before and after IVIG treatment. A decrease in IL‐2R levels in KD children following effective IVIG treatment was inversely associated with the pre‐treatment percentage of CD8 + T cells, indicating a significant suppression of cellular immunity prior to treatment 11 . In the presented study, children with IVIG retreatment often in a higher level of the IL‐2R by more than 2000 units compared with children with IVIG one dose (Table 2).…”

“…Several studies have reported that KD tends to occur more frequently in boys than in girls, although there was no obvious difference in the number observed between boys and girls with KD 1,3 . However, in previous studies, the number of enrolled patients was more in boys 11,28 . Therefore, it is important to consider the role of sex.…”

“…Cytokines including IL‐1, IL‐2, IL‐6, TNF‐α, IFN‐γ and so on have been studied in many researches of KD 17 . Previous investigations, including our own work, revealed that during the acute phase of KD and before treatment, a child's count of CD19 + B cells increases markedly and CD4 + T cells decreases significantly suggesting the predominance of humoral immunity 11,18,19 . Hyperactive cytokines and unbalanced distribution of lymphocyte subgroups constitute the inflammatory feature of KD.…”

“…Previous studies have established predictive models for children with KD at risk of IVIG resistance, identifying various risk factors including serum sodium, C‐reactive protein (CRP) and total bilirubin (TBil) and others 7–10 . However, there is significant variation in the identified independent risk factors for KD among children from different cities within the same region 7–11 . In addition, these prediction models tended to focus more on clinical features and indicators rather than on items associated with specific aspects of inflammation 11–15 .…”