Elevated Serum Interleukin-1β Levels in Male, but not Female, Collision Sport Athletes with a Concussion History

Abstract

It is increasingly reported that a history of concussion may be associated with chronic deleterious consequences. While the pathophysiology that contributes to these consequences is not well understood, neuroinflammation is postulated to be critical. Activation of multi-protein complexes termed inflammasomes, a key component of this inflammatory response, has been reported in more severe TBIs; however, it has not been investigated in milder TBIs, such as concussion. This study investigated serum levels of interleukin (IL)-1b and IL-18 (key proteins activated downstream of these inflammasomes) at acute, sub-acute, and chronic time-points post-concussion. We recruited 105 Australian footballers (65 male, 40 female) during the pre-season, then prospectively followed these players for the occurrence of concussion during the season. At baseline, 58 footballers reported a previous concussion history, and 47 reported no previous concussion history. Additionally, 25 players sustained a mid-season concussion and were sampled at 2, 6, and 13 days post-concussion. Serum levels of IL-1b and IL-18 were quantified using highly sensitive Simoa HD-X Analyzer assays. At baseline, IL-1b levels were higher in male, but not female, footballers with a previous concussion history compared with footballers with no concussion history. There was also a positive correlation between years of collision sport participation and IL-18 levels in males. No evidence was found in males or females to indicate that IL-1b or IL-18 levels differed at 2, 6, or 13 days postconcussion. These findings provide novel insights into potential sex-specific physiological consequences of concussion, and suggest that neuroinflammation may be persistent chronically following concussion in male athletes.

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

“…Similar alterations were found in saliva,49 50 urine,51 52 and CSF53 54 studies. There is conflicting evidence concerning the discriminatory ability for some biomarkers27 31 40 47 55–57 while others specifically failed to distinguish between SRC and controls 22 45 48 58–60. Multiple studies showed a mix of longitudinally altered biomarker trajectories that either resolved by symptom recovery/RTP/RTS23 29 33 45 61 while others were associated with prolonged recovery 18 30–32 42 48 53 54 62–64.…”

Apolipoprotein ɛ4 Status and Brain Structure 12 Months after Mild Traumatic Injury: Brain Age Prediction Using Brain Morphometry and Diffusion Tensor Imaging

“…In a study by Li et al, they investigated other assessment of biological age like DNA methylation age estimator (DNAmAge), physiological age, cognitive function, functional aging index (FAI), and frailty index (FI) and found that the largest effects of mortality risk were seen for methylation age estimators and the FI [62]. There are also other biomarkers of interest when it comes to MTBI and aging pathobiology, like inflammatory biomarkers such as interferons, cytokines, and interleukins [63,64], and biomarkers for oxidative stress [65] which should be investigated further in future studies.…”

Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players

“…A questionnaire was administered pertaining to factors including demographics (ie, age, gender, height, weight), sporting history (ie, sports played, age they commenced collision sports, age they commenced all sport, years participating in collision sport, years participating in all sports), years of education and history of concussion (number and dates of previous concussions). 4 , 24 - 29 The ‘sport concussion assessment tool’ (SCAT; SCAT3 for 2017/18 players, SCAT5 for 2019 players) assessed symptom severity (maximum 132) at 2-, 6- and 13-days after SRC.…”