Attenuation of delayed-type hypersensitivity by fullerene treatment

Abstract

Expansion and commercialization of nanotechnology mean that it is important to understand the potential health hazards of manufactured nanoparticles. Here, we focused on the effect of fullerene, a type of nanoparticle already in commercial use, on delayed-type hypersensitivity (DTH) induced by methyl-bovine serum albumin (mBSA). Delayed-type hypersensitivity was induced with methyl-bovine serum albumin in female C57BL/6 mice. A colloidal suspension of crystalline C60 (nano-C60; average particle size 165 nm; 200 μL; 5.5 μg/mL) was injected intravenously twice, just before immunization and challenge with mBSA. Nano-C60 treatment significantly attenuated footpad swelling, compared with that in DTH-disease control mice. Cytokine analysis indicated that nano-C60 treatment switched the cytokine balance towards Th1-dominance. Pro-inflammatory cytokines IL-6 and IL-17 were significantly increased in DTH mice, and these increases were significantly suppressed by nano-C60 treatment. Suppression of IL-17 by nano-C60 was confirmed in an in vitro splenocyte culture. However, production of TNF-α was increased in DTH mice, and the increase was significantly enhanced by nano-C60 treatment. The ratio of regulatory T (Treg) cells to total T (CD4+) cells was also significantly increased by nano-C60 treatment, compared with that in DTH-disease control mice. Nano-C60 treatment showed significant immunomodulatory effects in a mouse DTH model: IL-6 and IL-17 production was down-regulated, and the Treg cell ratio was up-regulated, concomitantly with attenuation of the pathology of DTH.