Inflammation After Anterior Cruciate Ligament Injury

Anterior cruciate ligament (ACL) injury causes a deleterious cascade of events including increased inflammation and cartilage breakdown. Increases in pro-inflammatory cytokines following injury begin almost immediately following ACL rupture and include upregulations in inflammatory pathways. New evidence is emerging that elucidates the proteomic response to ACL injury and demonstrates that the beginning stages of post-traumatic osteoarthritis (PTOA) are more similar to rheumatoid arthritis than idiopathic osteoarthritis. Furthermore, in-depth studies of ACL patient populations reveals a subset of patients that presents a dysregulated inflammatory response following injury. These patients have an increased inflammatory burden and a more robust pro-inflammatory reaction to acute injury. While this subset of patients does not represent all of those who will go on to develop PTOA, the differences in individualized inflammatory responses are important to consider in treatment. Moreover, ACL reconstruction surgery presents a second and potentially larger insult to the joint resulting in the re-initiation of inflammation and an increase in cartilage breakdown. This “second hit” triggers a sustained inflammatory response following surgery that does not return back to pre-operative levels and persists for at least 5 years after reconstruction. There are many factors to consider when determining treatment including the timing of treatment, dosing, and return to activity guidelines. Due to the large secondary hit from surgery, treatment post-operatively, rather than pre-operatively, will likely be more effective. Furthermore, extended-release treatment options and how loading may affect the inflammatory process during the resumption of physical activities should all be taken into consideration.