© 2004 American Thoracic Society
Peptide Therapy and AsthmaTo the Editor:We read with interest the editorial by Boulet (1) that accompanied our recent publication in the Journal (2). In his discussion of the therapeutic use of allergen-derived peptides, Dr. Boulet omits citations of findings from a number of our earlier studies that support the potential of peptide immunotherapy. Instead, he refers to earlier published data with different peptides (i.e., IPC 1 and IPC 2, which only covered chain I of Fel d 1 [3]). It is our contention that peptide therapy remains an exciting possibility. The majority of studies of peptide therapy for allergic diseases (3–7) have demonstrated some degree of clinical efficacy. It is important to pursue this avenue to refine treatment protocols and peptide preparations, thereby thoroughly evaluating the potential of the approach. In the studies we refer to, we demonstrated the induction of isolated late asthmatic reactions (LARs) after intradermal administration of short T cell peptide epitopes from a major allergen (Fel d 1) (8). Sampling at the height of the reaction (6 hours) by bronchoscopy, we determined that LARs induced by intradermal peptide administration did not appear to be accompanied by any cellular recruitment to the bronchial mucosa or the generation of enhanced levels of mediators known to be associated with bronchoconstriction (9). Furthermore, we also showed that intradermal administration of peptides was subsequently associated with the induction of hyporesponsiveness, both to the peptides and to the whole allergen (10). Observations in relation to the ability of peptides to induce hyporesponsiveness or "immunological tolerance" were further supported by a randomized, double-blind, placebo-controlled trial in which Fel d 1 peptide administration to cat allergens was shown to markedly modulate T cell responses in vitro, to significantly reduce the magnitude of both early and late cutaneous reactions to whole allergen challenge, and to improve toleration of cats (4). Finally, we would like to shed further light on the mechanisms underlying the peptide-induced LARs. In a recent unpublished study, to analyze mucosal changes, we subjected cat allergic asthmatic subjects who were experiencing an inhaled peptide–induced LAR to bronchoscopy with endomucosal biopsy and alveolar lavage. Our results suggest that the only significant increase in cell numbers in the mucosa is in the CD4+ T cell compartment, and that despite the detection of mild sputum eosinophilia in the recently published study (2), eosinophils were not significantly increased in bronchoalveolar lavage or bronchial mucosa during (6-hour time point) peptide-induced LARs.
Imperial College London London, United Kingdom FOOTNOTES Conflict of Interest Statement: M.L. has acted as a consultant to Powderject Pharmaceuticals PLC in the field of peptide vaccine development for allergic diseases and received $80,000 in consultancy fees from June 2002–present; he is a coinvestigator on a grant from Powderject Pharmaceuticals PLC with a value of approximately $800,000, and received approximately $160,000 after the sale of Powderject Pharmaceuticals PLC to Chiron Vaccines; A.B.K. has acted as a consultant to Powderject Pharmaceuticals PLC in the field of peptide vaccine development for allergic diseases and received $106,000 in consultancy fees from June 2002–present; he is a coinvestigator on a grant from Powderject Pharmaceuticals PLC with a value of approximately $800,000, and received approximately $300,000 after the sale of Powderject Pharmaceuticals PLC to Chiron Vaccines. REFERENCES
From the Author: I would like to thank Drs. Larché and Kay for their comments on my editorial about their recent study on late asthmatic reactions induced by inhalation of allergen-derived T cell peptides, and, in particular, for providing additional information and some unpublished data on this matter (1, 2). It is not possible to make an exhaustive review of the topic in the limited space of an editorial. I therefore chose to report what I considered some of their previous key observations on intradermal administration of peptides and mostly focus the discussion on the effects of inhaled peptides (2–4). I can understand their enthusiasm about the possibilities of peptide therapy, but they also admit that its clinical efficacy has been up to now relatively modest. I nevertheless did stress in my editorial that "future studies are needed to further explore this important field of research," although their data showed that the inhaled route has some limitations that could make this route of administration unsuitable for such treatment.
In the study reported by Oldfield and coworkers (5), multiple injections of T cell peptides derived from Fel d 1 to patients allergic to cats led to a reduction in early- and late-phase allergic reactions to whole allergens and modulated the production of interleukin (IL)-4, IL-10, IL-13, and INF- I therefore agree that various observations, including many coming from the group of Drs. Larché and Kay, whom I acknowledge as having made a major contribution to this field, show that peptide therapy can modulate immune responses to peptides and allergens. However, the clinical significance of these observations and the exact role of peptide immunotherapy remain to be determined.
Institut de Cardiologie et de Pneumologie de l'Université Laval Quebec City, Quebec, Canada FOOTNOTES Conflict of Interest Statement: L.-P.B. has served as an advisor and participated in educational and research activities of most pharmaceutical companies involved in asthma care and to various national respiratory societies and governmental committees. REFERENCES
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