Interleukin-1 receptor antagonist suppresses contact hypersensitivity.
Interleukin-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of interleukin-1 (IL-1), blocks IL-1 binding to its receptors but has no agonistic activity. IL-1 is thought to play an important role in contact hypersensitivity (CHS), although the effects of exogenously administered IL-1 in CHS have been somewhat controversial. To clarify the role of IL-1 in CHS, we studied the effect of IL-1 receptor blockade using exogenous IL-1ra and evaluated these effects on CHS. We examined the in vivo effects of local administration of recombinant human IL-1ra in the murine CHS model. Local injection of IL-1ra to sensitized BALB/c mice just before challenge with dinitrofluorobenzene resulted in a significant reduction in the intensity of CHS responses, assessed by ear swelling. A dose-response study revealed that maximal inhibition of ear swelling (36% to 43%) was observed after intradermal injection of IL-1ra at doses of 10 to 100 micrograms/ear. This reduction in ear swelling in IL-1ra-injected ears consisted of less inflammatory cell infiltration and decreased edema in the dermis compared with controls. Suppression of CHS was observed when IL-1ra was applied in the 24-h interval preceding challenge with dinitrofluorobenzene, whereas no suppressive 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 before sensitization also suppressed CHS responses. However, IL-1ra injection did not suppress phenol-induced inflammation. These results suggest that IL-1ra is an effective inhibitor of both the sensitization and elicitation phases of CHS expression in mice, thus emphasizing the role of IL-1 as an immunologic potentiator of responses associated with CHS.
Kondo
S
S
Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Canada.
Pastore
S
S
Fujisawa
H
H
Shivji
G M
GM
McKenzie
R C
RC
Dinarello
C A
CA
Sauder
D N
DN
D000818:Animals; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000503:physiopathology; D003875:Drug Eruptions / Q000188:drug therapy; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D051379:Mice; D008807:Mice, Inbred BALB C; D019800:Phenol; D010636:Phenols; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D010636:Phenols; D012795:Sialoglycoproteins; D019800:Phenol