Figure 1.

The inflammation amplifier. (A) Image of the activation of the inflammation amplifier in the presence and absence of NE. A combination of IL-17 and IL-6 causes a synergistic effect on the induction of inflammation-amplifier target chemokines such as CCL20 in non-immune cells including fibroblasts, endothelial cells, and certain synovial cells. NE further enhances the chemokine production. Other neurotransmitters can also influence activation of the inflammation amplifier. See Arima et al. (2012) for the original data. (B) The synergistic effect seen in (A) requires the concomitant activation of two transcriptions factors, NF-kB and STAT3. In the case of autoimmune diseases, Th-17 derived IL-17 induces an initially low amount of IL-6 from non-immune cells via NF-κ B activation. Secreted IL-6 together with IL-17 forms a positive feedback loop to produce excessive expression of the target genes including many inflammatory chemokines such as CCL20, CCL2, etc. Consequently, various immune cells are recruited at the region around the target cells via chemokine expression, and inflammation takes place. Persistent activation of the inflammation amplifier, as is the case in F759 mice, drives chronic inflammation. IL-7, a target of the amplifier and derived from non-immune cells, fuels the proliferation, and survival of Th17 cells. The activation of the inflammation amplifier can be modulated by regional neural activation.