Nitric oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury. Inflammation as a possible cause of elevated no metabolites.

Background: This article investigates nitric oxide (NO) metabolism following severe head injury (SHI). We wished to clarify the alterations of NO metabolism end products that is associated with SHI, and to delineate the role of inflammation in this process.

Methods: In a prospective study, we simultaneously measured the concentrations of NO metabolites and interleukin-8 (IL-8) in the ventricular cerebrospinal fluid (CSF) of 11 patients who had suffered SHI. The CSF concentrations of nitrite (NO(-)(2)) and nitrate (NO(-)(3)) combined, and of IL-8 were measured during the following four time periods post-trauma: 6 to 10, 20 to 28, 40 to 56, and 64 to 74 hours. Levels were measured using the corresponding kits.

Results: Compared to the ventricular CSF control values, all of our SHI patients had significantly elevated CSF levels of NO(-)(2) plus NO(-)(3) (NO(-)(2) + NO(-)(3)) and IL-8 during all periods tested. CSF NO(-)(2) + NO(-)(3) and IL-8 concentrations reached their maximums simultaneously at 20 to 28 hours following trauma (Spearman's rank correlation = 0.609, p < 0.05), and NO(-)(2) + NO(-)(3) levels were significantly higher than those measured at 6 to 10, 40 to 56, and 64 to 74 hours. [Nitrite-nitrate concentrations: 6-10 hours: 19.22 +/- 6.75, 20-28 hours: 25 +/- 6.2 micromol/l, 40-56 hours: 19.82 +/- 4.47, and 64-74 hours: 19.72 +/- 4.61 micromol/l, (p < 0.05). IL-8 concentrations: 6-10 hours: 3,232 +/- 2,976.2, 20-28 hours: 3,458.45 +/- 3,048 pg/mL, 40-56 hours: 2,616.41 +/- 2,539.21, 64-74 hours: 1,388.88 +/- 1,216.7 pg/mL, (p < 0.001).]. This simultaneous surge in NO(-)(2) + NO(-)(3) and IL-8 in the initial 24 hours post-traumatic indicated that inflammation secondary to SHI increased the rate of NO metabolism, resulting in higher levels of metabolites in the CSF.

Conclusion: In patients with SHI, CSF concentrations of the dominant metabolites of NO are elevated in the first 3 days after trauma. A similar concurrent spike in the CSF level of IL-8, a marker of acute inflammatory response, can also be demonstrated. These data indicate that the predominant cause of the higher CSF NO(-)(2) + NO(-)(3) concentrations observed in SHI is most likely inflammation.