Cytokine Responses in Severe Traumatic Brain Injury: Where There Is Smoke, Is There Fire?

This scoping review will discuss the basic functions and prognostic significance of the commonly researched cytokines implicated in severe traumatic brain injury (sTBI), including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), transforming growth factor-β (TGF-β), substance P, and soluble CD40 ligand (sCD40L). A scoping review was undertaken with an electronic search for articles from the Ovid MEDLINE, PUBMED and EMBASE databases from 1995 to 2017. Inclusion criteria were original research articles, and reviews including both animal models and human clinical studies of acute (< 3 months) sTBI. Selected articles included both isolated sTBI and sTBI with systemic injury. After applying the inclusion criteria and removing duplicates, 141 full-text articles, 126 original research articles and 15 review articles, were evaluated in compiling this review paper. A single reviewer, CC, completed the review in two phases. During the first phase, titles and abstracts of selected articles were reviewed for inclusion. A second evaluation was then conducted on the full text of all selected articles to ensure relevancy. From our current understanding of the literature, it is unlikely a single biomarker will be sufficient in accurately prognosticating patients with sTBI. Intuitively, a more severe injury will demonstrate higher levels of inflammatory cytokines which may correlate as a marker of severe injury. This does not mean, necessarily, these cytokines have a direct and causal role in the poor outcome of the patient. Further research is required to better delineate the complex systemic inflammatory and CNS interactions that occur during sTBI before they can be applied as a reliable prognostic tool.