IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta 1 and blood-brain barrier function

Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been assoc iated with adverse outcome. In order to elucidate the potential role of ant i-inflammatory mediators, the production of interleukin-10 (IL-10) was moni tored in paired cerebrospinal fluid (CSF) and serum of 28 patients with sev ere traumatic brain injury (TBI) and compared to control samples. The patte rn of IL-10 was analyzed with respect to the patterns of IL-6, tumor necros is factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using t he CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI pa tients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was si milar in both fluids, showing a peak during the first days and a second, lo wer rise in the second week. Intrathecal IL-10 synthesis is hypothesized si nce CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, I L-10-index (CSF/serum-IL-10/Q(A)) was elevated in 23 individuals, and eleva tion of CSF-IL-10 showed to be independent from severe BBB dysfunction. Nei ther CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta 1 showed similar patterns in CSF over time, where as rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain da mage. (C) 1999 Elsevier Science B.V. All rights reserved.