Figure 2.

Mechanisms by which interleukin 1 (IL-1) and tumor necrosis factor (TNF) can directly regulate neuronal synaptic function.

(a) (A) IL-1 and TNFα regulate the excitatory and inhibitory neurotransmitter balance. Hyperphysiological levels of cytokines, such as following a traumatic brain injury (TBI), increase excitatory (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMAPR) and N-methyl-D-aspartic acid receptor (NMDAR)) neurotransmission, while decreasing inhibitory (γ-aminobutyric acid (GABA) A receptor (GABA_AR)) neurotransmission. Cytokines can also affect the release of glutamate (Glu) from neurons, and the uptake and release of glutamate from astrocytes. (B) IL-1 and TNFα also increase the activity of the serotonin transporter (SERT), leading to a decrease in serotonin (5-HT) at the synapse. (C) Members of the IL-1 family of proteins are also involved in synapse formation and stabilization, and IL-1 signaling can regulate this process. EAAT2: Excitatory amino acid transporter 2; IL-1R1: IL-1 receptor 1; IL-1RAPL1: IL-1-receptor accessory protein like 1; IL-1RAcP: IL-1 receptor accessory protein; TNFR1: TNF receptor 1; JNK: c-Jun terminal kinase; system X_C ^-: cystine/glutamate antiporter system.