Fig. 5.

Cytokine intracellular signaling pathways. Cytokines bind to transmembrane allosterically regulated proteins. Upon ligand binding, the intracellular signaling pathways that are activated correlate to their ability to alter behavior. Three classic proinflammatory cytokines – TNFα, IL-1β and IL-6 – activate cascades leading to NF-κB and MAPK (p38 and JNK) activation. The MAPK cascade is enhanced by parallel signaling pathways that produce ceramide. In contrast, IFNγ, IFNα/β and IL-6 signal primarily through the JAK/STAT pathway. The NF-κB, MAPK and JAK/STAT pathways are considered proinflammatory, inducing a feed-forward cytokine inflammatory response. The ceramide-generating and MAPK pathways have distinct enhancing and inhibitory effects on neuron excitation.