Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects.
We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.
Simons
F E
FE
Health Sciences Clinical Research Centre, Faculty of Medicine, University of Manitoba, Canada.
Imada
M
M
Li
Y
Y
Watson
W T
WT
HayGlass
K T
KT
D000328:Adult; D000818:Animals; D001249:Asthma / Q000628:therapy*; D002415:Cats / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D012220:Rhinitis / Q000276:immunology / Q000628:therapy*; D012882:Skin Tests / Q000379:methods*
D016207:Cytokines; D006023:Glycoproteins; D010446:Peptide Fragments; C059296:Fel d 1 protein, Felis domesticus