Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells.

Abstract

The neuropeptide substanceP(SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1receptor(NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate(NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP. In the present study, we investigated the anti-inflammatory effects of ketamine on the SP-induced activation of a human astrocytoma cell line, U373MG, which expresses high levels of NK-1R. The results from our experiments indicated that ketamine suppressed the production of interleukin(IL)-6 and IL-8 by the U373MGcells. Furthermore, ketamine inhibited the SP-induced activation of extracellular signal‑regulated kinase(ERK)1/2, p38mitogen-activated protein kinase(MAPK) and nuclear factor-κB(NF-κB). Taken together, these observations suggest that ketamine may suppress the SP-induced activation(IL-6 and IL-8 production) of U373MGcells by inhibiting the phosphorylation of signaling molecules(namely ERK1/2, p38MAPK and NF-κB), thereby exerting anti‑inflammatory effects. Thus, ketamine may modulate SP-induced inflammatory responses by NK-1R‑expressing cells through the suppression of signaling molecules(such as ERK1/2, p38MAPK and NF-κB).