Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice.
Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interleukin-1 receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painful neuropathy. Here we investigated whether combined therapy with epineurial anti-TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a chronic constrictive injury of one sciatic nerve were treated epineurially with neutralizing antibodies to either IL-1R1 or TNF alone or with a combined application of neutralizing antibodies to TNF and IL-1R1. Combined treatment with anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and mechanical allodynia more effectively than monotherapy with either antibody. There were no detectable differences in IL-1beta and TNF endoneurial protein expression between animals with monotherapy and combined treatment. We conclude that combined anti-cytokine therapy may be a useful strategy in the treatment of neuropathic pain.
Schäfers
M
M
Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
Brinkhoff
J
J
Neukirchen
S
S
Marziniak
M
M
Sommer
C
C
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000276:immunology / Q000628:therapy; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000276:immunology / Q000628:therapy*; D010525:Peripheral Nerves / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000906:Antibodies; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha