Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons

O Obreja, W Biasio, M Andratsch, KS Lips, PK Rathee… - Brain, 2005 - academic.oup.com
O Obreja, W Biasio, M Andratsch, KS Lips, PK Rathee, A Ludwig, S Rose-John, M Kress
Brain, 2005academic.oup.com
The pro-inflammatory cytokine interleukin-6 (IL-6) together with its soluble receptor (sIL-6R)
induces and maintains thermal hyperalgesia. It facilitates the heat-induced release of
calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Here we
report that exposure of nociceptive neurons to the IL-6–sIL-6R complex or the gp130-
stimulating designer IL-6–sIL-6R fusion protein Hyper-IL-6 (HIL-6) resulted in a potentiation
of heat-activated inward currents (Iheat) and a shift of activation thresholds towards lower …
Abstract
The pro-inflammatory cytokine interleukin-6 (IL-6) together with its soluble receptor (sIL-6R) induces and maintains thermal hyperalgesia. It facilitates the heat-induced release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Here we report that exposure of nociceptive neurons to the IL-6–sIL-6R complex or the gp130-stimulating designer IL-6–sIL-6R fusion protein Hyper-IL-6 (HIL-6) resulted in a potentiation of heat-activated inward currents (Iheat) and a shift of activation thresholds towards lower temperatures without affecting intracellular calcium levels. The Janus tyrosine kinase inhibitor AG490, the selective protein kinase C (PKC) inhibitor, bisindolylmaleimide 1 (BIM1), as well as rottlerin, a selective blocker of the PKCδ isoform, but not the cyclooxygenase inhibitor indomethacin, effectively reduced the effect. Reverse transcription–polymerase chain reaction (RT–PCR) and in situ hybridization revealed expression of mRNA for the signal-transducing β subunit of the receptor gp130 in neuronal somata, rather than satellite cells in rat dorsal root ganglia. Together, the results suggest that IL-6–sIL-6R acts directly on sensory neurons. It increases their susceptibility to noxious heat via the gp130/Jak/PKCδ signalling pathway.
Oxford University Press