Synergistic Effect of Tolerogenic Dendritic Cells and Etanercept on a Collagen-induced Arthritis Animal Model

Abstract

The aim of this study was to determine the potential for an additive effect from combining treatments with tolerogenic dendritic cells (tDCs) and etanercept (ETN) in a case of established type II collagen-induced arthritis (CIA). CIA mice were treated with type II collagen-pulsed tDCs either alone or in combination with ETN. We compared the effects of monotherapy with tDCs or ETN with the effect of combination treatment on the resultant rheumatoid arthritis using histopathological analyses and measurements of paw volumes, regulatory T cell populations, and cytokine levels. The clinical and histologic analysis revealed an additive effect from the combination therapy. Monotherapy with tDCs showed a tendency to ameliorate arthritis symptoms, while monotherapy with ETN reduced the paw swelling at 3 days after administration, but was not effective toward the end of the experimental period. The combined treatment group also showed a marked inducement of the regulatory T cells and Th2 cytokines that are affected by tDCs compared with those of either untreated or ETN-treated CIA mice. ETN administered in combination with tDCs provided a substantially higher level of clinical benefit at the cellular level to CIA mice than the administration of either of these agents alone.