International Journal of Biological Sciences

Impact factor

ISSN 1449-2288

News feeds of IJBS published articles
Manuscript login

open access Global reach, higher impact

Journal of Genomics in PubMed Central. Submit manuscript now...


International Journal of Medical Sciences

Journal of Cancer

Journal of Genomics


Journal of Bone and Joint Infection (JBJI)


Journal of Biomedicine

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2012; 8(9):1267-1280. doi:10.7150/ijbs.4828


The Pathological and Physiological Roles of IL-6 Amplifier Activation

Masaaki Murakami1✉, Toshio Hirano2✉

1. Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan;
2. JST-CREST, Osaka University, Osaka, Japan.


The NFκB-triggered positive feedback loop for IL-6 signaling in type 1 collagen+ non-immune cells (IL-6 amplifier) was first discovered to be a synergistic signal that is activated following IL-17A and IL-6 stimulation in type 1 collagen+ non-immune cells. Subsequent disease models have shown that it can also be stimulated by the simultaneous activation of NFκB and STAT3, functions as a local chemokine inducer, and acts as a mechanism for local inflammation, particularly chronic ones like rheumatoid arthritis and a multiple sclerosis. Moreover, we have recently shown that hyper activation of the IL-6 amplifier via regional neural activation establishes a gateway for immune cells including autoreactive T cells to pass the blood-brain barrier at dorsal vessels in 5th lumbar cord. Here we review how the IL-6 amplifier is activated by neural activation and the physiological relevance of the gateway to the central nervous system. Accumulating evidences continues to suggest that the IL-6 amplifier offers a potential molecular mechanism for the relationship between neural activation and the development of inflammatory diseases, which could establish a new interdisciplinary field that fuses neurology and immunology.

Keywords: IL-6, neural activation, inflammatory diseases

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Murakami M, Hirano T. The Pathological and Physiological Roles of IL-6 Amplifier Activation. Int J Biol Sci 2012; 8(9):1267-1280. doi:10.7150/ijbs.4828. Available from