Background Insulin-like growth factor binding protein 3 (IGFBP-3) is known to interfere NF-κB signaling pathway and thereby has an anti-inflammatory function.
Objectives Due to the central role of NF-κB in rheumatoid arthritis (RA) development, we postulated that IGFBP3 could have anti-arthritic effects.
Methods An adenovirus containing IGFBP3 cDNA (Ad-IGFBP3) was used to deliver IGFBP3 to collagen-induced arthritis (CIA) mice through an intraarticular injection into the ankle joints of the CIA mice.
Results Mice with CIA had an increased incidence of disease and developed experimental arthritis in the hind paws. In contrast, in mice injected with Ad-IGFBP3, the severity of arthritis based on clinical scores, hind paw thickness, and radiological and pathological findings was significantly attenuated. In addition, Ad-IGFBP3 down-regulated local and systemic levels of pro-inflammatory cytokines compared with control virus-injected mice. The protective effects of Ad-IGFBP3 were mediated by the inhibition of the NF-κB signaling pathway.
Conclusions These results suggest that blocking the NF-κB pathway by Ad-IGFBP3 in rheumatoid joints reduces tissue destruction. Therefore, the development of an immunoregulatory strategy based on IGFBP3 may have therapeutic potential for the treatment of rheumatoid arthritis.
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Disclosure of Interest None Declared
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