We previously demonstrated a significant association between IL-18 gene polymorphism 105 A/C and asthma. In this study, we investigated the relationship of IL-18 gene polymorphism to IL-18 production capability by monocytes. The frequency of gene polymorphisms including IL-18-105 A/C and IL-18--137G/C was determined by PCR analyses. The IL-18 production by monocytes stimulated without or with LPS or A23187 + PMA for 1 day was measured by ELISA. The produced IL-18 spontaneously or in response to A23187 + PMA by monocytes was significantly higher for Volunteers with 105 A/A genotype than with 105 A/C genotype. Similarly, the production capability of IL-18 by monocytes from Volunteers with -137 G/G genotype was significantly higher than that with -137 G/C genotype and significant linkage disequilibrium was observed between 105 A/C and -137 G/C polymorphism. Thus, the genetic capacity to produce more IL-18 in response to stimuli may affect the onset of asthma. (c) 2006 Elsevier Inc. All rights reserved.