Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression.
The chronic constriction injury model of mononeuropathy is a direct, partial nerve injury yielding thermal hyperalgesia. The inflammation that results from this injury is believed to contribute importantly to both the neuropathological and behavioral sequelae. This study involved administering a single dose (250 ng) of interleukin-10 (IL-10), an endogenous anti-inflammatory peptide, at the site and time of a chronic constriction injury (CCI) lesion to determine if IL-10 administration could attenuate the inflammatory response of the nerve to CCI and resulting thermal hyperalgesia. In IL-10-treated animals, thermal hyperalgesia was significantly reduced following CCI (days 3, 5 and 9). Histological sections from the peripheral nerve injury site of those animals had decreased cell profiles immunoreactive for ED-1, a marker of recruited macrophages, at both times studied (2 and 5 days post-CCI). IL-10 treatment also decreased cell profiles immunoreactive for the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) at day 2, but not day 5. Qualitative light microscopic assessment of neuropathology at the lesion site did not suggest substantial differences between IL-10 and vehicle-treated sections. The authors propose that initial production of TNF-alpha and perhaps other proinflammatory cytokines at the peripheral nerve lesion site importantly influences the long-term behavioral outcome of nerve injury, and that IL-10 therapy may accomplish this by downregulating the inflammatory response of the nerve to injury.
Wagner
Rochelle
R
Department of Anesthesiology, VA Medical Center and the University of California, San Diego, CA 92093-0629,USA Department of Pathology (Neuropathology), VA Medical Center and the University of California, San Diego, CA 92093-0629, USA.
Janjigian
Michael
M
Myers
Robert R
RR
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D003250:Constriction; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10