Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue.
In a model of closed head injury (CHI) in the rat we have shown the activation of phospholipase A2 and the production of eicosanoids after injury: at 15 min, mainly 5-hydroxyeicosatetraenoic acid (5-HETE), and at 24 h, mainly prostaglandin E2. The present study was designed to test whether CHI can also trigger the production of cytokines in the brain. CHI was induced in ether-anesthesized rats by a weight-drop device falling over the exposed skull covering the left hemisphere, 1-2 mm lateral to the midline in the midcoronal plane. In the posttraumatic period (1-24 h), the rats were decapitated, cortical tissue from the injured zone of the contused and contralateral hemispheres was removed and sonicated, and cytokine activity was assessed. Whereas no tumor necrosis factor alpha (TNF alpha) activity was found in normal brain tissue, it was detectable in the contused hemisphere (approximately of 72 +/- 50 pg/mg protein) as early as 1 h post-CHI. TNF alpha levels increased at 2 h, peaked at 4 h, (approximately of 609 +/- 540 pg/mg protein), and declined thereafter. At parallel intervals, only low levels of TNF alpha were detected in the contralateral hemisphere. In normal brain, interleukin-6 (IL-6) was nondetectable. Following CHI, high levels of IL-6 were present, although their accumulation lagged behind that of TNF alpha by 2-4 h, peaking at 8 h (62 +/- 31 ng/mg protein). We suggest that the rapid production of TNF alpha and IL-6 following CHI is a local inflammatory response of brain tissue to primary insult.
Department of Pharmacology, Hebrew University--Hadassah Medical School, Jerusalem, Israel.
E
E
Shohami
M
M
Novikov
R
R
Bass
A
A
Yamin
R
R
Gallily
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha