Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood-brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62-12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800-7,900 pg/ml) induced greater NGF production in cultured astrocytes (202-434 pg/ml) than samples with low IL-8 (600-1,000 pg/ml), which showed a smaller NGF increase (0-165 pg/ml). Anti-IL-8 antibodies strongly reduced (52-100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0-52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor alpha and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.

To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock. IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels. IL-8 was detected in all 27 CSF samples. Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant. Serum IL-8 levels were highest in patients with a symptom history < 12 h. The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF. IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical stimulation of the vagus nerve suppresses pro-inflammatory cytokine release in response to endotoxin, I/R injury, and hypovolemic shock and protects against lethal hypotension. To determine the effect of vagus nerve stimulation on coagulation pathways, anesthetized pigs were subjected to partial ear resection before and after electrical vagus nerve stimulation. We observed that electrical vagus nerve stimulation significantly decreased bleeding time (pre-electrical vagus nerve stimulation = 1033 ± 210 s versus post-electrical vagus nerve stimulation = 585 ± 111 s; P < 0.05) and total blood loss (pre-electrical vagus nerve stimulation = 48.4 ± 6.8 mL versus post-electrical vagus nerve stimulation = 26.3 ± 6.7 mL; P < 0.05). Reduced bleeding time after vagus nerve stimulation was independent of changes in heart rate or blood pressure and correlated with increased thrombin/antithrombin III complex generation in shed blood. These data indicate that electrical stimulation of the vagus nerve attenuates peripheral hemorrhage in a porcine model of soft tissue injury and that this protective effect is associated with increased coagulation factor activity.

No abstract

Nitric monoxide (NO) exerts a great variety of physiological functions. L-Arginine supplies amino groups which are transformed to NO in various NO-synthase-active isoenzyme complexes. NO-synthesis is stimulated under various conditions increasing the tissue of stable NO-metabolites. The major oxidation product found is nitrite. Elevated nitrite levels were reported to exist in a variety of diseases including HIV, reperfusion injury and hypovolemic shock. Denitrifying bacteria such as Paracoccus denitrificans have a membrane bound set of cytochromes (cyt cd1, cyt bc) which were shown to be involved in nitrite reduction activities. Mammalian mitochondria have similar cytochromes which form part of the respiratory chain. Like in bacteria quinols are used as reductants of these types of cytochromes. The observation of one-e- divergence from this redox-couple to external dioxygen made us to study whether this site of the respiratory chain may also recycle nitrite back to its bioactive form NO. Thus, the aim of the present study was therefore to confirm the existence of a reductive pathway which reestablishes the existence of the bioregulator NO from its main metabolite NO2-. Our results show that respiring mitochondria readily reduce added nitrite to NO which was made visible by nitrosylation of deoxyhemoglobin. The adduct gives characteristic triplet-ESR-signals. Using inhibitors of the respiratory chain for chemical sequestration of respiratory segments we were able to identify the site where nitrite is reduced. The results confirm the ubiquinone/cyt be1 couple as the reductant site where nitrite is recycled. The high affinity of NO to the heme-iron of cytochrome oxidase will result in an impairment of mitochondrial energy-production. "Nitrite tolerance" of angina pectoris patients using NO-donors may be explained in that way.