An investigation of plasma interleukin-6 in sport-related concussion.

BACKGROUND: Increasing evidence suggests inflammation is an important component of concussion pathophysiology. However, its etiology, restitution, and potential clinical repercussions remain unknown. The purpose of the current study was to compare the blood concentrations of interleukin (IL) -6, a prominent inflammatory cytokine, between healthy athletes and athletes with a sport-related concussion (SRC), while addressing the potential confounds of sex, recent physical activity, and the interacting effect of concussion history. METHOD: A prospective, observational cohort study was conducted on athletes at a single academic institute participating across 13 interuniversity sports. Follow-up of 96 athletes who agreed to provide a blood sample was completed: 41 athletes with a physician diagnosed SRC, and 55 healthy athletes. Ella™, the high sensitivity immunoassay system by ProteinSimple was used to measure peripheral plasma concentrations of IL-6 within the first week (median = 4 days, range = 2-7) following injury. A resampled ordinary least squares regression was used to evaluate the relationship between IL-6 concentrations and concussion status, while partial least squares regression was used to evaluate the relationship between IL-6 and both symptom burden and time to clinical recovery. RESULTS: Regression analysis identified a negative relationship between plasma IL-6 concentrations and the interaction between an acute SRC and a history of concussion (ß = -0.29, p = 0.029). IL-6 did not differ between healthy athletes and those with an acute SRC independent of concussion history, and was not correlated with either recovery time or symptom burden in athletes with SRC. CONCLUSION: Perturbations to circulating IL-6 concentrations, a key inflammatory cytokine, may be more pronounced following SRC in athletes who have a history of concussion. These results add to a growing body of evidence supporting the involvement of inflammation at all phases of recovery following SRC, and potentially support a concomitant effect of prior concussion on acute SRC pathophysiology.

The relationship between symptom burden and systemic inflammation differs between male and female athletes following concussion.

BACKGROUND: Inflammation appears to be an important component of concussion pathophysiology. However, its relationship to symptom burden is unclear. Therefore, the purpose of this study was to evaluate the relationship between symptoms and inflammatory biomarkers measured in the blood of male and female athletes following a sport-related concussion (SRC). RESULTS: Forty athletes (n = 20 male, n = 20 female) from nine interuniversity sport teams at a single institution provided blood samples within one week of an SRC. Twenty inflammatory biomarkers were quantitated by immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms. Partial least squares (PLS) analyses were used to evaluate the relationship(s) between biomarkers and symptoms. In males, a positive correlation between interferon (IFN)-γ and symptom severity was observed following SRC. The relationship between IFN-γ and symptoms was significant among all symptom clusters, with cognitive symptoms displaying the largest effect. In females, a significant negative relationship was observed between symptom severity and cytokines IFN-γ, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO); a positive relationship was observed between symptom severity and MCP-4. Inflammatory mediators were significantly associated with all symptom clusters in females; the somatic symptom cluster displayed the largest effect. CONCLUSION: These results provide supportive evidence of a divergent relationship between inflammation and symptom burden in male and female athletes following SRC. Future investigations should be cognizant of the potentially sex-specific pathophysiology underlying symptom presentation.

Peripheral blood neuroendocrine hormones are associated with clinical indices of sport-related concussion.

The purpose of this study was to evaluate the relationship between neuroendocrine hormones and clinical recovery following sport-related concussion (SRC). Ninety-five athletes (n = 56 male, n = 39 female) from a cohort of 11 interuniversity sport teams at a single institution provided blood samples; twenty six athletes with SRC were recruited 2-7 days post-injury, and 69 uninjured athletes recruited prior to the start of their competitive season. Concentrations of seven neuroendocrine hormones were quantitated in either plasma or serum by solid-phase chemiluminescent immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms at the time of blood sampling in all athletes. Multivariate partial least squares (PLS) analyses were used to evaluate the relationship between blood hormone concentrations and both (1) time to physician medical clearance and (2) initial symptom burden. A negative relationship was observed between time to medical clearance and both dehydroepiandrosterone sulfate (DHEA-S) and progesterone; a positive relationship was found between time to medical clearance and prolactin. Cognitive, somatic, fatigue and emotion symptom clusters were associated with distinct neuroendocrine signatures. Perturbations to the neuroendocrine system in athletes following SRC may contribute to initial symptom burden and longer recovery times.