THE PIVOTAL ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE DEVELOPMENT OF INFLAMMATORY HYPERALGESIA

1 The hyperalgesic activities in rats of interleukin-1beta (IL-1beta), IL-6, IL-8, tumour necrosis factor alpha (TNFalpha) and carrageenin were investigated. 2 IL-6 activated the previously delineated IL-1/prostaglandin hyperalgesic pathway but not the IL-8/sympathetic mediated hyperalgesic pathway. 3 TNFalpha and carrageenin activated both pathways. 4 Antiserum neutralizing endogenous TNFalpha abolished the response to carrageenin whereas antisera neutralizing endogenous IL-1beta, IL-6 and IL-8 each partially inhibited the response. 5 The combination of antisera neutralizing endogenous IL-1beta + IL-8 or IL-6 + IL-8 abolished the response to carrageenin. 6 These results show that TNFalpha has an early and crucial role in the development of inflammatory hyperaglesia. 7 The delineation of the roles of TNFalpha, IL-1beta, IL-6 and IL-8 in the development of inflammatory hyperalgesia taken together with the finding that the production of these cytokines is inhibited by steroidal anti-inflammatory drugs provides a mechanism of action for these drugs in the treatment of inflammatory hyperalgesia.