The aims of the present study were to establish to what extent IL-1, and intracellular pathways involving mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB), play a role in ultrafine particle-induced release of IL-6 by primary rat epithelial lung cells. Ultrafine carbon black (Printex 90) induced a concentration- and time-dependent increase in the release of IL-1alpha, IL-1beta and IL-6. The ultrafine carbon black-induced release of IL-6 was completely eliminated by an IL-1 receptor antagonist (IL-1ra). Cellular release of IL-1alpha, IL-1beta and IL-6 was significantly attenuated by curcumin and by inhibitors of the MAPKs ERK1/2 (PD98069), p38 (SB202190) and JNK (SP600125), whereas pyrrolidine dithiocarbamate (PDTC) attenuated the release of IL-6, but not of IL-1alpha and IL-1beta. The effects of curcumin and PDTC may indicate an involvement of NF-kappaB. Furthermore, ultrafine carbon black induced degradation of IkappaBalpha, used as an indicator of NF-kappaB activation, and induced phosphorylation of ERK1/2, p38 and JNK1/2. This degradation and phosphorylation was attenuated by IL-1ra. The present findings provide more insight into the largely unknown mechanisms involved in ultrafine particle-induced release of cytokines from lung cells. The findings suggest that ultrafine carbon black-induced release of IL-6 strongly depends on IL-1 and that activation of MAPKs and NF-kappaB is involved in this response.