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CSF-1 in inflammatory and arthritic pain development


Saleh, R; Lee, MC; Khiew, SH; Louis, C; Fleetwood, AJ; Achuthan, A; Forster, I; Cook, AD; Hamilton, JA
2018-08-17
Journal of Immunology
Journal Article
201
7
2042-2053
Pain is one of the most debilitating symptoms in many diseases for which there is inadequate management and understanding. CSF-1, also known as M-CSF, acts via its receptor (CSF-1R, c-Fms) to regulate the development of the monocyte/macrophage lineage and to act locally in tissues to control macrophage numbers and function. It has been implicated in the control of neuropathic pain via a central action on microglia. We report in this study that systemic administration of a neutralizing anti-CSF-1R or CSF-1 mAb inhibits the development of inflammatory pain induced by zymosan, GM-CSF, and TNF in mice. This approach also prevented but did not ameliorate the development of arthritic pain and optimal disease driven by the three stimuli in mice, suggesting that CSF-1 may only be relevant when the driving inflammatory insults in tissues are acute and/or periodic. Systemic CSF-1 administration rapidly induced pain and enhanced the arthritis in an inflamed mouse joint, albeit via a different pathway(s) from that used by systemic GM-CSF and TNF. It is concluded that CSF-1 can function peripherally during the generation of inflammatory pain and hence may be a target for such pain and associated disease, including when the clinically important cytokines, TNF and GM-CSF, are involved. Our findings have ramifications for the selection and design of anti-CSF-1R/CSF-1 trials.
ASI
Inflammation
10.4049/jimmunol.1800665
30120124
Refer to copyright notice on published article.

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Creation Date 2018-10-11 04:23:18 Last Modified 2018-10-12 03:43:51