INTERLEUKIN-6 AND TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNAS ARE INDUCED IN RAT FACIAL NUCLEUS FOLLOWING MOTONEURON AXOTOMY

Transection of the rat facial nerve leads to a rapid activation of both astrocytes and microglia around axotomized motoneurons. The factors involved in glial activation in vivo are poorly defined but cytokines have been implicated as major regulators of glial activity in vitro. In the present study we have investigated the expression of cytokine mRNAs in the axotomized facial nucleus that might be involved in glial activation. Eight hours after axotomy unilateral transection of the facial nerve had already induced a rapid accumulation of interleukin (IL)-6-mRNA, with a peak at 24 hours. No IL-6 mRNA was detected on the unoperated control side. Transforming growth factor (TGF)-beta1 mRNA was detected at low levels in the normal facial nucleus, increasing to three times the normal level 2 days after axotomy. After day 7 TGF-beta1 mRNA levels gradually declined, with a second minor peak 21 days after axotomy. In situ hybridization experiments, 4 and 21 days after axotomy, localized TGF-beta1 mRNA to activated microglial cells around regenerating motoneurons, as well as probably some astrocytes. Motoneurons did not express TGF-beta1 mRNA. TGF-beta3 was found to be normally expressed in the facial nucleus but was not regulated by axotomy. No mRNA for IL-1, tumour necrosis factor-alpha or interferon-gamma was found in the regenerating facial nucleus at any point in time. Our data indicate that IL-6 might act as an early activating signal for glial cells in response to motoneuron axotomy, and that TGF-beta1 expressed by activated glial cells might provide a long-lasting negative feedback signal to control glial activation.