Immunomodulation - A Cure for Allergic Disease?
Immunomodulation – Therapy of the Future?
Stephen I. Wasserman
La Jolla, California
Dr. Stephen Wasserman was born in Los Angeles, California in 1942. He received his undergraduate degree from Stanford Univ. and his MD from UCLA. Dr. Wasserman trained in Internal Medicine and Allergy and Immunology at Harvard. Dr. Wasserman served on the faculty of Harvard Medical School until 1979 when he moved to develop the Allergy and Immunology program at the University of California, San Diego (UCSD). At UCSD he became Chairman of the Department of Medicine (1986-2000) and held the Helen M. Ranney Chair from 1988-2001. He is currently Professor of Medicine, and Director of the training program in Allergy and Immunology at UCSD. Dr. Wasserman has published over 200 scientific articles and book chapters with particular focus on human allergic disorders. His research has been both at the bench, and in small and larger scale clinical trials with particular attention to the cells and mediators of immediate hypersensitivity, human asthma, and models of physical allergy.
Dr. Wasserman has served as Chairman of the American Board of Allergy and Immunology, and the American Board of Internal Medicine, and as President of the American Academy of Allergy, Asthma and Immunology.
Modulation of the immune response to allergens has been the goal of physicians treating allergic disorders for over a century. Initial attempts to do so became the basis for our current methods of immunotherapy of inhalant mediated allergic disease. The use of small and gradually increasing parenterally administered doses of allergen has been shown to increase allergen specific IgG, to decrease allergen specific IgE, and to lead to modification of the T-lymphocyte responses to allergen. Some of these changes are associated with alteration in cytokine production, with particular importance of IL-10 having been recently demonstrated. Advances in our understanding of the mechanism by which the host becomes sensitized to allergen to generate IgE antibodies has led to a wide array of possible new approaches to modulate the human immune system to prevent allergic disease.
Additional approaches for immunomodulation include:
Prevention of allergy by:
- Avoidance of allergen in the susceptible host, initiated at or even before birth
- Encounter with allergen early in life in appropriate dose or route to engender tolerance
- Encounter with allergen in the context of innate immune signals early in life to engender tolerance (probiotics, endotoxin, pets)
Eradication of allergy by:
- Manipulating T-lymphocyte development to favor Th-1 responses (T-bet vs. Gata-3)
- Augmenting regulatory T-lymphocyte responses (CD4+/CD25+, Th3, Treg)
- Altering dendritic cell processes to educate T-lymphocytes toward Th-1 bias (IL-10)
- Alteration of mast cell responsiveness (anti-IgE, inhibition of signalling)
- Use of non-anaphylactic modified allergens for systemic immunotherapy (B/T cell selective antigens, synthetic mimeotopes)
- Traditional allergens under anti-IgE protection
- Novel routes of allergen immunotherapy (sublingual, oral, rectal)
- Administration of allergen/antigen in the presence of protective cytokines or in conjunction with antibodies to Th-2 promoting cytokines, or both
- Use of novel adjuvants (CPG)