Platelet-derived mitochondrial preparation did not alter early inflammatory markers in a bilateral lipopolysaccharide-induced model of equine synovitis.

The research investigated the impact of injecting autologous platelet-derived mitochondrial preparation into horse joints suffering from synovitis, a type of inflammation. The study found no significant evidence that this treatment was able to reduce the inflammation.

Research Design

• The study used a bilateral lipopolysaccharide (LPS)-induced model of equine synovitis. Six horses suffering from this condition were observed over a period of three months.
• 2ng of LPS, a potent inflammatory agent, was injected into the bilateral intercarpal joints of these horses. This step was designed to heighten the inflammation, providing a clear model of synovitis.
• The researchers also injected mitochondria, isolated using a commercial kit, into one joint of each horse. The opposite joint received a vehicle control, establishing a within-subject control mechanism.

Outcomes

• The appearance of the mitochondrial organelles was studied using transmission electron microscopy. The researchers also measured a range of outcomes, including synovial fluid and whole-blood cytology, cytokine levels in the serum and synovial fluid, and gene expression levels in synovial fluid leukocytes.
• These measures were taken at several time points – 0, 4, 8, 24, and 48 hours.
• To evaluate the data, the research team used linear mixed-effects models and nonparametric tests when normality assumptions were not met.

Results

• No significant differences were observed between the treated and control joints in terms of synovial fluid cytology, cytokine expression, or gene expression.
• The LPS injections increased the number of nucleated cells in the synovial fluid, demonstrating its expected inflammatory effect.
• Systemic changes were also observed – specifically, an elevation in IL-12 and reduction in IL-10. In the synovial fluid, FGF-2 decreased, while interferon-γ, various interleukins, and tumor necrosis factor-α (TNF-α) increased compared to baseline.
• The study also observed upregulation in the gene expression of several proteins, including C-X-C motif chemokine ligand 1, IL-1β, IL-5, IL-6, IL-18, matrix metallopeptidase 13, and PTEN-induced kinase 1, while OPA1 mitochondrial dynamin-like GTPase and TNF-α were downregulated over time.

Conclusions

• The study found that this model of LPS-induced synovitis produced minimal systemic inflammation and moderate local joint inflammation. However, there was no discernible benefit from the mitochondrial preparation.
• Though the conceptual potential for mitotherapy (the use of mitochondria for therapeutic purposes) exists, this particular study design failed to demonstrate any benefits from this approach in reducing the inflammatory effects of LPS-induced synovitis.