Lack of interleukin-17 leads to a modulated micro-environment and amelioration of mechanical hypersensitivity after peripheral nerve injury in mice.
Interleukin-17 (IL-17) is involved in a wide range of inflammatory disorders and in recruitment of inflammatory cells to injury sites. A recent study of IL-17 knock-out mice revealed that IL-17 contributes to neuroinflammation and neuropathic pain after peripheral nerve injury. Surprisingly, little is known of micro-environment modulation by IL-17 in injured sites and in pathologically related neuroinflammation and chronic neuropathic pain. Therefore, we investigated nociceptive sensitization, immune cell infiltration, myeloperoxidase (MPO) activity, and expression of multiple cytokines and opioid peptides in damaged nerves of wild-type (IL-17(+/+)) and IL-17 knock-out (IL-17(-/-)) mice after partial sciatic nerve ligation. Our results demonstrated that the IL-17(-/-) mice had less behavioral hypersensitivity after partial sciatic nerve ligation, and inflammatory cell infiltration and pro-inflammatory cytokine (tumor necrosis factor-α, IL-6, and interferon-γ) levels in damaged nerves were significantly decreased, with the levels of anti-inflammatory cytokines IL-10 and IL-13, and expressions of enkephalin, β-endorphin, and dynorphin were also decreased compared to those in wild-type control mice. In conclusion, we provided evidence that IL-17 modulates the micro-environment at the level of the peripheral injured nerve site and regulates progression of behavioral hypersensitivity in a murine chronic neuropathic pain model. The attenuated behavioral hypersensitivity in IL-17(-/-) mice could be a result of decreased inflammatory cell infiltration to the injured site, resulting in modulation of the pro- and anti-inflammatory cytokine milieu within the injured nerve. Therefore, IL-17 may be a critical component for neuropathic pain pathogenesis and a novel target for therapeutic intervention for this and other chronic pain states.
Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC Graduate Institutes of Clinical Medical Sciences, Chang Gung University, Linkou, Taiwan, ROC Department of Anesthesiology, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, ROC.
Yuan-Ji
YJ
Day
Jiin-Tarng
JT
Liou
Chiou-Mei
CM
Lee
Yi-Chiao
YC
Lin
Chih-Chieh
CC
Mao
An-Hsun
AH
Chou
Chia-Chih
CC
Liao
Hung-Chen
HC
Lee
D000818:Animals; D001522:Behavior, Animal; D059333:Central Nervous System Sensitization / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D006930:Hyperalgesia / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D059225:Nociception; D059348:Peripheral Nerve Injuries / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
D016207:Cytokines; D004745:Enkephalins; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D018793:Interleukin-13; D020381:Interleukin-17; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001615:beta-Endorphin; D004399:Dynorphins; D009195:Peroxidase
Animal model; Inflammation; Interleukin-17; Nerve injury; Neuropathic pain