CLOSED-HEAD INJURY TRIGGERS EARLY PRODUCTION OF TNF-ALPHA AND IL-6 BYBRAIN-TISSUE

In a model of closed head injury (CHI) in the rat we have shown the ac tivation of phospholipase A(2) and the production of eicosanoids after injury: at 15 min, mainly 5-hydroxyeicosatetraenoic acid (5-HETE), an d at 24 h, mainly prostaglandin E(2). The present study was designed t o test whether CHI can also trigger the production of cytokines in the brain. CHI was induced in ether-anesthesized rats by a weight-drop de vice falling over the exposed skull covering the left hemisphere, 1-2 mm lateral to the midline in the midcoronal plane. In the posttraumati c period (1-24 h), the rats were decapitated, cortical tissue from the injured zone of the contused and contralateral hemispheres was remove d and sonicated, and cytokine activity was assessed. Whereas no tumor necrosis factor alpha (TNF alpha) activity was found in normal brain t issue, it was detectable in the contused hemisphere (similar to 72 +/- 50 pg/mg protein) as early as 1 h post-CHI. TNF alpha levels increase d at 2 h, peaked at 4 h, (similar to 609 +/- 540 pg/mg protein), and d eclined thereafter. At parallel intervals, only low levels of TNF alph a were detected in the contralateral hemisphere. In normal brain, inte rleukin-6 (IL-6) was nondetectable. Following CHI, high levels of IL-6 were present, although their accumulation lagged behind that of TNF a lpha by 2-4 h, peaking at 8 h (62 +/- 31 ng/mg protein). We suggest th at the rapid production of TNF alpha. and IL-6 following CHI is a loca l inflammatory response of brain tissue to primary insult.