GP130 CYTOKINES, LEUKEMIA INHIBITORY FACTOR AND INTERLEUKIN-6, INDUCENEUROPEPTIDE EXPRESSION IN INTACT ADULT-RAT SENSORY NEURONS IN-VIVO -TIME-COURSE, SPECIFICITY AND COMPARISON WITH SCIATIC-NERVE AXOTOMY

The gp130 cytokines leukemia inhibitory factor and interleukin-6 are n euroactive cytokines associated with peripheral nerve injury. Here we show that exogenous administration of these factors selectively regula tes neuropeptide phenotype in intact sensory neurons in a manner consi stent with their role as injury-induced factors. Intraneural injection of leukemia inhibitory factor into the intact sciatic nerve of adult rats induces a significant increase in the percentage of neuronal prof iles immunoreactive for galanin in the L4 and L5 dorsal root ganglia w ithout altering the percentage profiles immunoreactive for vasoactive intestinal polypeptide or neuropeptide Y. Galanin-immunoreactivity was predominantly confined to those neurons which retrogradely transporte d and accumulated leukemia inhibitory factor. The up-regulation of gal anin-immunoreactivity observed in L4 and L5 dorsal root ganglia follow ing unilateral axotomy of the sciatic nerve was significantly reduced following continuous treatment for two weeks with a monoclonal antibod y against the gp130 receptor motif. Intraneural injection of interleuk in-6 into the intact sciatic nerve also significantly increased the pe rcentage of neuronal profiles which displayed galanin-immunoreactivity but not vasoactive intestinal polypeptide or neuropeptide Y-immunorea ctivity, Our results indicate that cytokines which interact with the g p130 receptor at the site of peripheral nerve injury contribute to the cell body response to axotomy. Changes in the levels of such cytokine s however are insufficient to account for the complete repertoire of n europeptide phenotypic chan peripheral nerve injury. (C) 1998 IBRO. Pu blished by Elsevier Science Ltd.