Cerebrospinal Fluid Concentrations of Anti-Inflammatory Mediators in Early-Phase Severe Traumatic Brain Injury

Abstract

In our previous study of patients with early-phase severe traumatic brain injury (TBI), the anti-inflammatory interleukin (IL)-10 concentration was lower in cerebrospinal fluid (CSF) than in serum, whereas proinflammatory IL-1beta and tumor necrosis factor (TNF)-alpha concentrations were higher in CSF than in serum. To clarify the influence of additional injury on this disproportion between proinflammatory and anti-inflammatory mediators, we compared their CSF and serum concentrations in patients with severe TBI with and without additional injury. All 35 study patients (18 with and 17 without additional injury) had a Glasgow Coma Scale score of 8 or less upon admission. With the exception of additional injury, clinical characteristics did not differ significantly between groups. CSF and serum concentrations of two proinflammatory mediators (IL-1beta and TNF-alpha,) and three anti-inflammatory mediators (IL-1 receptor antagonist [IL-1ra], soluble TNF receptor-I [sTNFr-I], and IL-10) were measured and compared at 6 h after injury. CSF concentrations of proinflammatory mediators were much higher than the corresponding serum concentrations in both patient groups (P < 0.001). In contrast, serum concentrations of anti-inflammatory mediators were much higher than the paired CSF concentrations in patients with additional injury (P < 0.001), but serum concentrations were lower than or equal to the corresponding CSF concentrations in patients without additional injury. CSF concentrations of IL-1beta, IL-1ra, sTNFr-I, and IL-10 were significantly higher (P < 0.01 for all) in patients with high intracranial pressure (ICP; n = 11) than in patients with low ICP (n = 24), and were also significantly higher (P < 0.05 for all) in patients with an unfavorable outcome (n = 14) than in patients with a favorable outcome (n = 21). These findings indicate that increased serum concentrations of anti-inflammatory mediators after severe TBI are mainly due to additional extracranial injury. We conclude that anti-inflammatory mediators in CSF may be useful indicators of the severity of brain damage in terms of ICP as well as overall prognosis of patients with severe TBI.

Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier

“…Using the primary cultures of choroidal epithelial cells, we found that the rate of apical secretion of CCL2 in response to IL-1b is relatively stable during the first 6 hours of incubation with the cytokine (see Figure 3B) and amounts to 15 ng/h per cm 2 of surface area of epithelial monolayer. In these experiments, the epithelial monolayers were exposed to 10 pg/mL of IL-1b, the average concentration of IL-1b found in ventricular CSF in patients with severe TBI at 6 hours after injury (Shiozaki et al, 2005). To extrapolate these in vitro data to the in vivo situation, we assumed that the apical surface of choroidal epithelium of one lateral ventricle CP is 0.7 cm 2 (without taking into account the surface area of apical microvilli; unpublished data).…”

Traumatic Brain Injury and Inflammation: Emerging Role of Innate and Adaptive Immunity

“…Elevated levels of IL-1b were also detected intrathecally in patients with head injury (Winter et al, 2002). Moreover, these elevated levels were correlated to poorer clinical outcome (Chiaretti et al, 2005;Shiozaki et al, 2005). The proinflammatory cytokines IL-1a and IL-1b are believed to initiate inflammation and to contribute to neurodegeneration after various brain insults including TBI, whereas IL-1ra seemed to be neuroprotective.…”

Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury

“…A number of groups have investigated the relationship between cytokine protein measurements, including TNFa, in the CSF with outcome after TBI in relatively small cohorts without demonstrating evidence of a correlation between high TNFa levels and poor outcome. 46,47 It has been shown, however, that serum and CSF TNFa correlate with the occurrence of the secondary complications of intracranial hypertension and decreased cerebral perfusion pressure. 48,49 Alterations in other cytokines have also been studied after TBI with increases in IL-1b and IL-6 correlating with poor outcome 50 or without a clear relationship to outcome.…”