Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor.
The late-phase allergic reaction (LPR) occurs 4 to 8 h after allergen exposure and probably causes the symptoms of chronic allergic disease. To determine the effects of soluble IL-1 receptor on the cutaneous LPR, we performed a prospective, randomized, double-blind, placebo-controlled study on 15 allergic subjects. Intradermal injections of allergen were placed on subjects' forearms, followed by immediate subcutaneous injections at the same site of either 1, 10, 25, 50, or 100 micrograms of rhu IL-1R to three subjects in each dosage group. Placebo was given to matched allergen-injected sites on the contralateral arm. Erythema, induration, and itching were recorded for each site. Sites were biopsied at 8 h for immunohistologic evaluations. Rhu IL-1R significantly reduced the clinical reaction at all concentrations. At 1 and 10 micrograms, measurements of LPR were significantly less (p < 0.05) than at placebo sites at several time points from 2 to 8 h. At higher concentrations, LPR was suppressed at rhu IL-1R and placebo sites, suggesting a systemic effect of rhu IL-1R. Histologic evaluation and indirect immunofluorescence for eosinophil granule major basic protein, neutrophil elastase, and mast cell tryptase showed no statistical differences between rhu IL-1R and placebo sites or among doses. IL-1 plays an important role in the generation of allergic LPR. While microgram quantities of rhu IL-1R inhibited the clinical signs and symptoms of LPR, its effects on the allergic inflammatory infiltrate are yet to be defined. In this short term trial, rhu IL-1R was neither immunogenic nor toxic.
Mullarkey
M F
MF
Department of Medicine, Swedish Hospital Medical Center, Seattle, WA 98104.
Leiferman
K M
KM
Peters
M S
MS
Caro
I
I
Roux
E R
ER
Hanna
R K
RK
Rubin
A S
AS
Jacobs
C A
CA
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000917:Antibody Formation; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use*; D012867:Skin / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins