INTERLEUKIN-1 RECEPTOR ANTAGONIST SUPPRESSES CONTACT HYPERSENSITIVITY

Interleukin-1 receptor antagonist (IL-1ra), a naturally occurring inhi bitor of interleukin-1 (IL-1), blocks IL-1 binding to its receptors bu t has no agonistic activity, IL-1 is thought to play an important role in contact hypersensitivity (CHS), although the effects of exogenousl y administered IL-1 in CHS have been somewhat controversial. To clarif y the role of IL-1 in CHS, we studied the effect of IL-1 receptor bloc kade using exogenous IL-1ra and evaluated these effects on CHS, We exa mined the in vivo effects of local administration of recombinant human IL-1ra in the murine CHS model. Local injection of IL-1ra to sensitiz ed BALB/c mice just before challenge with dinitrofluorobenzene resulte d in a significant reduction in the intensity of CHS responses, assess ed by ear swelling, A dose-response study revealed that maximal inhibi tion of ear swelling (36% to 43%) was observed after intradermal injec tion of IL-1ra at doses of 10 to 100 mu g/ear. This reduction in ear s welling in IL-1ra-injected ears consisted of less inflammatory cell in filtration and decreased edema in the dermis compared with controls, S uppression of CHS was observed when IL-1ra was applied in the 24-h int erval preceding challenge with dinitrofluorobenzene, whereas no suppre ssive effect was observed when IL-1ra was applied 48 h before or after the challenge, Local administration of IL-1ra to naive mice 5 h befor e sensitization also suppressed CHS responses. However, IL-1ra injecti on did not suppress phenol-induced inflammation. These results suggest that IL-1ra is an effective inhibitor of both the sensitization and e licitation phases of CHS expression in mice, thus emphasizing the role of IL-1 as an immunologic potentiator of responses associated with CH S.