Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease

Abstract

To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs). Serum Th1 and Th2 cytokines, including interferon-γ (IFNγ), tumor necrosis factor α (TNFα), interleukin-10 (IL-10), IL-6, IL-4, and IL-2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre-IVIG, at 3 days after temperature normalization following IVIG treatment [post-IVIG], and 1 month posttreatment). Levels of IL-6, IL-10, TNFα, and IFNγ were significantly increased in KD patients pre-IVIG. Post-IVIG, the levels of IL-6, IL-10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post-IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post-IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL-4, IL-6, IL-10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post-IVIG levels of IL-6 and IL-10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre-IVIG, an IL-10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post-IVIG, an IL-6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL-10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs. Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.