Acute local and systemic effects of intra-articular administration of liposomal Ido-1 following anterior cruciate ligament rupture.

Joint injuries, such as rupture of the anterior cruciate ligament (ACL), are associated with the development of post-traumatic osteoarthritis (PTOA). ACL rupture can lead to disruption of metabolic pathways, including the conversion of tryptophan to kynurenine, which is associated with a sustained inflammatory response. An in vivo study was undertaken to determine the acute effects of intra-articular administration of liposomes loaded with the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-1 (IDO-1) following ACL rupture. Using a rat model of non-surgical ACL injury, male and female rats underwent a single intra-articular injection of empty liposomes, or liposomes loaded with IDO-1 and were subsequently randomized to 1- or 2-week endpoints. IDO-1 treatment after ACL injury was associated with a significant reduction in synovial fluid concentration of tryptophan at both 1- and 2-week endpoints. In addition to reduced tryptophan, IDO-1 treatment led to significantly lower synovial fluid concentrations of IL-1β and TNF-α. IDO-1-loaded liposomes also increased the ratio of regulatory T lymphocytes (Tregs) to IL-17-secreting helper T lymphocytes (Th17 cells). Similarly, IDO-1 treatment increased the number of CTLA4+ cells relative to IL-17 A+ cells that infiltrated joint tissues. Contrast-enhanced micro-computed tomography (CE-μCT) was used to quantify treatment-based effects on articular cartilage thickness and surface roughness at 2-week endpoint. In addition to sex-based differences, IDO-1-loaded liposome treatment was associated with increased cartilage thickness, with no significant effects on surface roughness. Later endpoints and more thorough histologic characterization is needed to determine whether this increased cartilage thickness represents a chondroprotective effect, or an anabolic effect.