Acute and long-term effects of IL-6 on cultured dorsal root ganglion neurones from adult rat.

IL-6 contributes to pain and hyperalgesia in inflamed tissue. We have investigated short- and long-term effects of IL-6 on dorsal root ganglion (DRG) neurones. Glycoprotein 130-like immunoreactivity (the signal transduction receptor subunit) was found in almost all neurones in DRG sections and in cultured DRG neurones from adult rat. In calcium-imaging studies bath application of IL-6 caused an increase of intracellular calcium in about one-third of the DRG neurones suggesting functional IL-6 receptors in a proportion of neurones. Long-term but not short-term exposure of DRG neurones to IL-6 in vitro significantly enhanced the proportion of DRG neurones expressing neurokinin 1 receptor-like immunoreactivity from 10% to up to 40%. This up-regulation was dependent on the activation of mitogen-activated protein kinase kinase (MEK) in the neurones, suggesting that the mitogen-activated protein kinase (MAPK) pathway is important for this effects of IL-6. Calcium-imaging studies demonstrated that previous exposure of DRG neurones to IL-6 enhanced the proportion of neurones that exhibit a substance P-induced rise in intracellular calcium. These data show that IL-6 has short- and long-term effects on a proportion of DRG neurones. These effects are likely to contribute to pro-nociceptive effects of IL-6.