Effects of NF-kappaB inhibitor on titanium particulate-induced inflammation in a murine model.
BACKGROUND
Activation of nuclear factor kappa B (NF-kappaB) signaling in response to implant particulates may be critical in the pathogenesis of implant loosening after joint arthroplasty. The purpose of this study was to investigate the inhibitory effects of pyrrolidine dithiocarbamate (PDTC) in a murine model of inflammation induced by titanium (Ti) particulates.


METHODS
Ti particulates were introduced into established air pouches on C57BL/6J mice. Mice were injected intraperitoneally with either high-dose PDTC (100 mg/kg) or low-dose PDTC (50 mg/kg). Mice without drug treatment, as well as mice injected with saline alone were included. Each group consisted of sixteen mice. The membranes and lavage fluid were harvested 2 d or 7 d after injection of particulate suspension for histological and molecular analysis.


RESULTS
Histologic analysis showed that PDTC reduced inflammatory responses in air pouches, that is, thinner membrane and decreased cellular infiltration. In addition, PDTC reduced the release of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the lavage fluid or supernatant of homogenates as evaluated by ELISA.


CONCLUSIONS
These results suggest that PDTC inhibits Ti particulate-induced inflammatory responses in the murine model; thus it represents a promising therapeutic candidate for the prevention and treatment of implant loosening.
Cheng
T'ao
T
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Zhang
Guo You
GY
Guo
Can Jie
CJ
Zhang
Xian'long
X
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013859:Thiocarbamates / Q000627:therapeutic use*; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D052638:Particulate Matter; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D011392:Proline; D014025:Titanium