Children with KD usually presents with acute phase symptoms including high fevers, elevated white counts and elevated sedimentation rates (ESR). High-dose intravenous immunoglobulin (IVIG) treatment rapidly abates these clinical symptoms. Moreover, recent immunological studies point to the role of superantigens in the pathogenesis of KD. Since interleukin-6 is a cytokine involved in the proinflammatory cascade which results in acute phase response and has also been shown to be upregulated in lymphocytes stimulated with superantigens, we sought to measure levels of this cytokine from sera that had been frozen on children with KD. IL-6 levels were measured by ELISA (R&D Systems, Minneapolis, MN) in pre-IVIG sera of 10 children with KD(mean±standard deviation: 3 years ±1.76; IL-6 level = 164.5 pg/ml ±108) and compared to sera from two sets of controls (10 children ages ≤ 2 years presenting with non-KD, non-bacterial febrile illness: mean±SD of IL-6 level = 5.99 pg/ml ±5.5 and in 10 healthy children ≤ 2 years without acute illness: IL-6 level = 1.26 pg/ml±0.5). The values of IL-6 in KD children were significantly higher by Wilcoxon Rank Sum Analysis (p<.01) over both sets of controls. Moreover, post-IVIG IL-6 levels in 5/5 available sera in children with KD who responded clinically to IVIG were lower (mean±SD of 42.8 pg/ml ±58), a 3.8 fold decrease in mean value from pre-IVIG level. No correlation was found using linear regression analysis between IL-6 levels versus ESR (r = 0.4) or IL-6 levels versus peak platelet counts (r = 0.13) with this small number of KD children. Conclusions Elevated IL-6 levels were measured in children with KD as compared to children of similar age in febrile and healthy states. Thus, IL-6 may play a role in the acute inflammatory response of this illness. Furthermore, IL-6 levels decreased in serum following IVIG administration. IL-6 (and other proinflammatory or superantigen-mediated response) attenuation by IVIG may play an important role in the rapid clinical improvement following IVIG treatment.
