Work

Antinociceptive interactions between excitatory interferon-γ and interleukin-17 in sensory neurons

Year: 2024

Type: article

Abstract: • The immune mediators Interferon- (IFN)γ and interleukin- (IL-)17 regulate nociception. • A large proportion of sensory neurons express IFNγ and IL-17 receptors. • The pronociceptive effect of IL-17 is inhibited by IFNγ. • Although inhibitory in vivo, IFNγ increases excitability of isolated sensory neurons. • TTX-sensitive Na + channels are involved in both excitatory and inhibitory IFNγ effects. Interferon-γ (IFNγ) and interleukin-17 (IL-17) are master regulators of innate and adaptive immunity. Here we asked whether these cytokines also regulate pain. Both cytokines increased the excitability of isolated small- to medium-sized sensory neurons, suggesting a pronociceptive effect. However, in vivo IL-17 was pronociceptive, whereas IFNγ was antinociceptive. Co-administration of IFNγ and IL-17 in vivo resulted in antinociception. Pre-incubation with IFNγ also eliminated the increase in excitability by interleukin-17A in isolated sensory neurons, demonstrating that the excitatory membrane effects of IFNγ can interfere with the excitatory membrane effects of IL-17, resulting in neuronal inhibition. IFNγ increased TTX-sensitive Na + currents, while IL-17 increased TTX-resistant Na + currents. Blocking TTX-sensitive Na + currents eliminated the inhibition of the IL-17 effect by IFNγ. We propose a novel form of inhibition in sensory neurons that allows the intrinsically excitatory IFNγ to attenuate pro-nociceptive effects of cytokines such as IL-17 through interactions with voltage-gated Na + currents.

Source: Brain Behavior and Immunity

DOI: 10.1016/j.bbi.2024.11.021