The Role of Interleukins in Pediatric Traumatic Brain Injury: A Narrative Synthesis

Traumatic brain injury (TBI) is a common and important cause of morbidity and mortality among pediatric patients, affecting 47-280 per 100,000 children every year. Head trauma can affect the brain not only by the injury itself but also via a neuroinflammatory process, which leads to blood-brain barrier (BBB) disruption, leukocyte infiltration, and edema formation. This process is regulated by several immune mediators, including interleukins (ILs), which are molecules that are currently investigated in both adult and pediatric TBI. In pediatric patients, IL-1β, IL-6, and IL-8 have mainly been investigated, while IL-10 and IL-17 also play a role in the neuroinflammatory cascade. Therefore, the purpose of this review was to examine the role of the aforementioned cytokines in the pathophysiology of pediatric TBI, as well as their role in determining clinical outcome and prognosis. IL-1β is a key pro-inflammatory cytokine in glutamate excitotoxicity post-TBI and in upregulating the expression of additional pro-inflammatory cytokines. Its high levels in cerebrospinal fluid (CSF) are correlated with injury severity and poor outcomes. IL-6 is an anti-inflammatory cytokine, and its concentration rises rapidly after the injury. Current data show that it can be useful in predicting severe TBI (sTBI) in addition to clinical parameters. IL-8 is a cytokine with several pro- and anti-inflammatory properties. On the one hand, it is a potent chemotactic agent, attracting inflammatory cells to the injured area, and it plays a role in BBB disruption. On the other hand, it promotes the survival of cholinergic and hippocampal neurons via the secretion of nerve growth factor (NGF). These cytokines are important in predicting the outcome of pediatric patients with TBI, as well as in predicting several post-TBI conditions such as fatigue and epilepsy, thus improving diagnostic ability and timely treatment. Further research, unraveling the complex mechanisms via which post-TBI neuroinflammation occurs, will lead to targeted therapies and better outcomes overall.