Attenuation of delayed-type hypersensitivity by fullerene treatment.
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 C(60) (nano-C(60); average particle size 165 nm; 200 microL; 5.5 microg/mL) was injected intravenously twice, just before immunization and challenge with mBSA. Nano-C(60) treatment significantly attenuated footpad swelling, compared with that in DTH-disease control mice. Cytokine analysis indicated that nano-C(60) 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-C(60) treatment. Suppression of IL-17 by nano-C(60) was confirmed in an in vitro splenocyte culture. However, production of TNF-alpha was increased in DTH mice, and the increase was significantly enhanced by nano-C(60) treatment. The ratio of regulatory T (Treg) cells to total T (CD4+) cells was also significantly increased by nano-C(60) treatment, compared with that in DTH-disease control mice. Nano-C(60) 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.
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Keichiro
K
Yamashita
Masanobu
M
Sakai
Naoya
N
Takemoto
Mitsutoshi
M
Tsukimoto
Katsumi
K
Uchida
Hiroshi
H
Yajima
Shigeru
S
Oshio
Ken
K
Takeda
Shuji
S
Kojima
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D037741:Fullerenes / Q000008:administration & dosage / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007275:Injections, Intravenous; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D012710:Serum Albumin, Bovine; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D037741:Fullerenes; D007155:Immunologic Factors; D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine