STUDIES OF IL-18 IN CHILDREN WITH REFRACTORY ATOPIC DERMATITIS

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Interleukin(IL)-18 is a proinflammatory cytokine and is now recognized an important regulator of both helper T cells(Th) 1 and 2 cytokine production. This study was performed to determine whether or not IL-18 is involved in the pathogeneses of refractory atopic dermatitis(AD) in childhood. Peripheral blood mononudear cells(PBMC) were obtained from children with refractory AD and control children who did not have any allergic disease, and then cultured with lipopolysaccharide(LPS) or phytohaemagglutinin(PHA). IL-18 secretion in the AD children(geometric mean (gm)=172 pg/ml) was significantly higher than that in non-allergic children(118 pg/ml). In contrast, interferon-gamma(IFN-γ) secretion in the AD children(gm=6.8 IU/ml) was significantly lower than that in non-allergic controls(gm=20.7 IU/ml).Since IL-18 has been known to synergize with IL-12 and IL-2 to induce IFN-γ synthesis, the inducing effect in vitro of combining IL-18 and IL-12 or IL-2 on IFN-γ production by PBMC was investigated. IFN-γ production was detected in all PBMCs from 20 non-allergic controls stimulated with IL-18+IL-12, however, the results for five of 21 AD children were under the detection limit for IFN-γ production. In collaboration with IL-2, IL-18 was able to induce IFN-γ production by PBMCs from all non-allergic children and 20 of 21 AD children, suggesting that impairment of the IL-12 signal cascade was involved in around a quarter of the AD children. For this reason, the CD4+ T cells were analyzed for IL-12 receptor expression with flow cytometry. The results were not statistically different between the AD children(6.5±1.9%) and the non-allergic children (6.1±1.1%) in IL-12 β-1 receptor expression on the T4+ cells. Unfortunately, the measurement for IL-12 β-2 receptor expression on CD4+ T cells has not been succeeded.