ABSTRACT
Role of mast cells in allergy had remained undetermined until the discovery of IgE in 1966. Then, IgE purified from many Liters of plasma, which had been donated from a patient with fatal myeloma, was distributed to researchers all over the world, and thus accelerated exploring the mechanisms involved in allergic reactions, particularly about the role of mast cells and basophils in the IgE-mediated reactions. Identification of mast cells as a progeny of a bone marrow hematopoietic stem cell in 1977 led us to successful in vitro culture of human mast cells. Along with the development of molecular biological techniques, the structure of the high affinity IgE receptor (FcεRI) was determined in 1989. These findings and subsequent investigations brought deeper understanding of IgE-mediated allergic diseases in the past half century, especially where mast cells are involved. We have now even obtained the information about whole genome expression of FcεRI-dependently activated mast cells. In sharp contrast to our comprehension of allergic diseases where IgE and mast cells are involved, the mechanisms involved in non-IgE-mediated allergic diseases or non-IgE-mediated phase of IgE-mediated diseases are almost left unsolved and are waiting for devoted investigators to reveal it.
Subject(s)
Hypersensitivity/history , Immunoglobulin E/history , Mast Cells/immunology , Animals , Cell Culture Techniques/history , Cytokines/genetics , Cytokines/history , Cytokines/metabolism , Genome-Wide Association Study , History, 20th Century , History, 21st Century , Humans , Hypersensitivity/genetics , Hypersensitivity/immunology , Hypersensitivity/metabolism , Immunoglobulin E/immunology , Interleukin-1/genetics , Interleukin-1/history , Mast Cells/classification , Mast Cells/metabolismABSTRACT
Although there has been a great amount of progress in the 25 years since the first reporting of the cDNA for IL-1alpha and IL-1beta, the history of IL-1 goes back to the early 1940s. In fact, the entire field of inflammatory cytokines, TLR and the innate immune response can be found in the story of IL-1. This Viewpoint follows the steps from the identification of the fever-inducing activities of "soluble factors" produced by endotoxin-stimulated leukocytes through to the discovery of cryopyrin and the caspase-1 inflammasome and on to the clinical benefits of anti-IL-1beta-based therapeutics. It also discusses some of the current controversies regarding the activation of the inflammasome. The future of novel anti-inflammatory agents to combat chronic inflammation is based, in part, on the diseases that are uniquely responsive to anti-IL-1beta, which is surely a reason to celebrate the 25th anniversary of the cloning of IL-1alpha and IL-1beta.
