Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand.
The effects of fluid percussion trauma on brain interleukin (IL)-6, IL-1 and tumor necrosis factor-alpha (TNF-alpha) levels have been studied. In the cortex and hippocampus of control and sham-operated rats, the levels of these cytokines were very low (below 4 units/mg protein) and constant. IL-6 and IL-1 levels in the ipsilateral cortex increased rapidly following trauma to reach a maximum of 350 and 16 units/mg protein, respectively, 8 h after the lesion, remained elevated until 18 h and decreased thereafter to basal values. TNF-alpha levels were maximally elevated (12 units/mg protein) at 3 h and 8 h and returned to basal values by 18 h. Qualitatively similar changes, but with 25-80-fold smaller amplitude, were seen in the contralateral cortex and in the ipsi- and contralateral hippocampus. The levels of IL-6 in the plasma of sham-operated and lesioned rats were only slightly elevated, whereas IL-1 and TNF-alpha were undetectable. Histological studies of brain tissue at early stages after trauma demonstrated an acute hemorrhage associated with neutrophil invasion. The administration of Ro5 4864 (0.5 mg/kg i.p.), a specific ligand of p (peripheral-type benzodiazepine) binding sites, did not result in any significant effect on the levels of IL-6, IL-1 or TNF-alpha in the brain of control or sham-operated animals. However, when administered 24 h before or 15 min after trauma, this benzodiazepine enhanced the increase of these cytokines by 2-4-fold in the ipsilateral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Taupin
V
V
INSERM U25, Hôpital Necker, Paris, France.
Toulmond
S
S
Serrano
A
A
Benavides
J
J
Zavala
F
F
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001930:Brain Injuries / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001570:Benzodiazepinones; D003292:Convulsants; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C028513:4'-chlorodiazepam