Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

Abstract

The balance of inflammation is critical to the repair of spinal cord injury (SCI), which is one of the most devastating traumas in human beings. Inflammatory cytokines, the direct mediators of local inflammation, have differential influences on the repair of the injured spinal cord. Some inflammatory cytokines are demonstrated beneficial to spinal cord repair in SCI models, while some detrimental. Various animal researches have revealed that local delivery of therapeutic agents efficiently regulates inflammatory cytokines and promotes repair from SCI. Quite a few clinical studies have also shown the promotion of repair from SCI through regulation of inflammatory cytokines. However, local delivery of a single agent affects only a part of the inflammatory cytokines that need to be regulated. Meanwhile, different individuals have differential profiles of inflammatory cytokines. Therefore, future studies may aim to develop personalized strategies of locally delivered therapeutic agent cocktails for effective and precise regulation of inflammation, and substantial functional recovery from SCI.

Keywords: inflammatory cytokines; local delivery; spinal cord injuries; therapeutic agents; tissue repair.

Figure 1

Local delivery of therapeutic agents, including direct administration, sustained‐release, cell transplantation and gene therapy, regulates inflammatory cytokines and promotes SCI repair. Cytokines in green are beneficial to SCI repair, while those in red are detrimental. Arrows indicate the regulation of inflammatory cytokines and promotion of repair.

Figure 2

Local delivery of flavopiridol nanoparticles increased GM‐CSF and decreased CXCL10 protein levels in spinal cord extracts in a rat right hemisection model. The right‐hemisection SCI model was established as previously described.188 0, 1, 7, or 21 days after injury, 0.5–1 cm spinal cord tissue at injury site was harvested and weighed before protein extraction. The protein levels were measured using a Procarta Multiplex Cytokine Immunoassay kit (Affymetrix, Fremont, CA). The protein levels were calculated as picogram per milligram spinal cord tissue. SCI, no treatment after injury. NP, local delivery of blank nanoparticles after injury. FLV, local delivery of flavopiridol nanoparticles after injury. n = 5. Data are mean ± standard deviation, *p < 0.05 versus NP, ^# p < 0.05 versus SCI.

Figure 3

The literature reviews of clinical use of local agent delivery to regulate inflammatory cytokines and treat SCI, using the search engines of both clinicaltrials.gov for the registry of clinical trials, and PubMed for the published clinical reports.