• Y Pang, L-W Fan, B Zheng, Z Cai, and P G Rhodes.
• Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
• Neuroscience. 2006 Aug 25; 141 (2): 745-755.

AbstractThere are increasing data in support of the hypothesis that inflammatory cytokines are involved in neonatal white matter damage. Despite extensive study of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, the role of interleukin-6 in the development of white matter damage is largely unknown. In the present study, the role(s) of interleukin-6 in mediating lipopolysaccharide-induced brain injury and behavioral changes was investigated by the intracerebral injection of lipopolysaccharide with interleukin-6 neutralizing antibody in the 5-day-old rat brain. Brain injury was examined in brain sections at postnatal day 8 and postnatal day 21. Behavioral tests including righting reflex, wire hanging maneuver, cliff avoidance, locomotor activity, gait analysis, responses in the elevated plus-maze and passive avoidance were performed from postnatal day 3 to postnatal day 21. Changes in astroglia, microglia and oligodendrocytes were studied using immunohistochemistry in the postnatal day 21 rat brain. Our results show that interleukin-6 antibody attenuated lipopolysaccharide-induced brain lateral ventricle dilation and improved neurobehavioral performance. Interleukin-6 antibody also suppressed lipopolysaccharide-induced astrogliosis and microglial activation, and increased the number of oligodendrocytes in white matter. However, no changes of tumor necrosis factor-alpha and interleukin-1beta were detected. In contrast, no histopathological changes and glial activation were observed in rats injected with only interleukin-6. The present study indicates that the contribution to brain injury by interleukin-6 depends on its interaction with other lipopolysaccharide-induced agents and not on interleukin-6 alone.

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