The purpose of this volume is to present what has been learned up to very recently in the application of advanced molecular biology in the understanding of immune-mediated mechanisms in the upper respiratory tract and inner ear. Thanks to new techniques, the nasopharyngeal mucosa has become a focus of attention on local immune responses, in order to use it clinically in vaccination therapy or in hyposensitization therapy for nasal allergies. In experimental otitis media, a number of investigators have found that cytokines are important determinants of both the pathogenesis and resolution of this disease. The immune system may also play a role in recurrent cholesteatoma. In examining the matrix, there has been found not only a high population of lymphocytes but the presence of Langerhans cells testifying to a stronger response to an antigen. More-over, immunohistochemical typing of peripheral skin samples revealed an increase in immunocompetent elements, particularly in patients who underwent the operation for a second recurrence of cholesteatoma. Clinical autoimmune inner ear disease, first reported in 1979, is now well known and has stimulated considerable research interest in the inner ear as an immunological target organ. Animal models of the disease have been developed in a number of laboratories, principally in the guinea pig and mouse. These studies demonstrated that heterologous as well as isologous inner ear antigen sensitization induces an autoimmune reaction in the inner ear, manifested by hearing loss, in degeneration of sensorineural tissue, antibody production, cellular infiltration, and IgG deposition, thus establishing the lesion as both cellular and humoral. Ultrastructural findings in the endolymphatic sac of a patient with active Menière's disease showing focal infiltration of intraepithelial reactive lymphocytes suggest an autoaggressive cellular reaction as the cause of the hydrops element in that disease. Lymphocytic infiltration has been observed in autoimmune thyroiditis, type I diabetes, systemic lupus, and chronic ulcerative colitis. Head and neck cancer research, particularly in squamous cell carcinoma, is blossoming and showing interesting progress in molecular biology. Cytokines IL-1a, IL-6, IL-8, and GM-CSF involved in deter-mining immune responsiveness and angiogenesis may prove to be useful prognostic markers and provide attractive targets for immune and anti-angiogenesis therapy, especially IL-2 and IL-12. However, biotherapies with vaccines, cytokines or other modalities designed to augment anti-tumor immune responses will not be effective until the cause and effect of tumor-related immune cell dysfunction and death are puzzled out. That day seems on the horizon. Clinical trials are already under way with IL-2 therapy of oral cavity and oropharyngeal squamous cell carcinoma under conventional treatment: cases with matched controls, showing treated patients with a longer disease-free survival time. This is a very welcome addition to the literature on immunobiology. It comprises a series of reports of prospective research done by the world's leading otorhinologic immunology laboratories and research teams, who present their latest accomplishments. Taken as a whole and severally, it is a splendid presentation of the state-of-the-art from the organ to the molecular biology level, serving both to give answers to many present enigmas and offer a springboard to future basic and mission-dedicated investigations.

Preface OTOLOGY - MIDDLE EAR 1. Early events in the development of middle ear inflammatory conditions as reflected by changes in the pars flaccida - A sequential experimental study Sten Hellström, Cecilia Mattsson and Per-Olof Eriksson 2. Cytokines contribute to inflammatory and immunological responses in experimental otitis media Allen F. Ryan, Paul Bikhazi and Antonino Catanzaro 3. Acute otitis media and pneumococcal vaccines - Immunological aspects Lieke A.M. Sanders, Reinier H. Veenhoven and Anne G.M. Schilder 4. Protection against bacterial acute otitis media Karin Prellner, Ann Hermansson, åsa Melhus and Peter White 5. Mucosal vaccination against otitis media Yuichi Kurono, Masashi Suzuki and Goro Mogi 6. T-cell mucosal immunity in the nasopharynx Hideyuki Kawauchi, Keisuke Sano, Hiromi Shiba, Chiaki Sano, Takaya Yamada and Tatsuo Suzuki 7. Is there a role for the immune system in recurrent cholesteatoma? Desiderio Passàli, Serena Petrillo, G.C. Passàli and Luisa Bellussi 8. The role of measles virus and heredity in the development of otosclerosis Michael J. McKenna and Arthur G. Kristiansen OTOLOGY - INNER EAR 9. Immunology of the inner ear - its relevance to human disease Jeffrey P. Harris, Elizabeth M. Keithley, Peter B. Billings, Grace S-Y. Yang, David W. Kim, Mien-Chi Chen, Allen Ryan and Gary Firestein 59 10. The search for the inner ear antigen of autoimmune sensorineural hearing loss Thomas E. Carey, Thankam S. Nair, Jennifer P. Gray, Hisham Zeitoun, Christopher D. Lansford, Susan G. Fisher, David F. Dolan, Yehoash Raphael, Josef M. Miller, Anna Ramakrishnan, David S. Lee, E. Dawn Denny, H. Alexander Arts, Steven A. Telian, Hussam El-Kashlan, Michael J. Disher, Robert T. Sataloff and Kristen Yeom 11. The endolymphatic duct and sac with emphasis on inner ear immunology Helge Rask-Andersen, Ulla Friberg, Birgitta Jansson and Niklas Danckwardt-Lillieström 12. Immune mediated sensorineural hearing loss with or without endolymphatic hydrops - A combined immuno-histophysiological and electrocochleographic approach Jan E. Veldman, Henk Bouman, Sjaak F.L. Klis, John C.M.J. de Groot and Guido F. Smoorenburg 13. An animal model for autoimmune inner ear disease Shun-ichi Tomiyama, Ken Jinnouchi, Tesuo Ikezono and Ruby Pawankar 14. Animal models for immune-mediated inner ear disease - Cell transfer studies Bertrand Gloddek, Silke Lassmann, Wolfgang Arnold and Jutta Gloddek RHINOLOGY 15. Nasal seroproteins: a new frontier in the exploration of physiology and pathology of nasal and sinus disease Robert I. Henkin, Amy Doherty and Brian M. Martin 16. The cytokine network in allergic rhinitis and polyposis åke Davidsson 17. Bacterial-mucin interaction in the upper aerodigestive tract shows striking heterogeneity - Implications in otitis media, sinusitis and pneumonia Joel M. Bernstein and Molakala Reddy 18. The role of glucocorticosteroids in sinonasal disease - Infection and inflammation: a vicious circle Pontus Stierna, Urban Knutsson, Tomas Norlander and Karin Forsgren 19. Pathophysiology of nasal mucosal swelling in nasal allergy Tsutomu Numata, Akiyoshi Konno, Nobuhisa Terada, Toyoyuki Hanazawa and Hiroshi Nagata 20. New approach to basophil histamine release for the diagnosis of allergic reactions Georges M. Halpern, Thomas M. Li and Kris J. Kontis 21. Viral upper respiratory tract infections - Immunological aspects Paul B. van Cauwenberge, Muriel J.P. van Kempen and Claus Bachert 22. Immunological aspects of Wegener's granulomatosis Valerie J. Lund and Geraldine Cambridge HEAD & NECK - ONCOLOGY 23. Immunological determinants as predictors for prognosis in patients with head and neck cancer T.P.U. Wustrow 24. Mechanisms of immune effector cell-tumor cell interaction - Impact on tumor progression Theresa L. Whiteside, Torsten E. Reichert, Brian R. Gastman, Takao Saito, Iris Kuss, Grzegorz Dworacki and Hannah Rabinowich 25. Cytokines in the immune pathogenesis and therapy of head and neck cancer Carter van Waes, Zhong Chen, Matthew Callister, Iris Colon, Nerian Ortiz, Conrad Smith, Giovana R. Thomas and Gang Dong 26. Combined treatment with interleukin-2 of operable oral cavity and oropharynx squamous cell carcinoma Giorgio Cortesina, Antonella de Stefani, Antonio Usai, Patrizia Mola, Walter Lerda and Riccardo Ragona 27. Locoregional immunotherapy in head and neck squamous cell carcinoma C.M.L. van Herpen, V. Mattijssen, L.T.M. Balemans, W. den Otter and P.H.M. de Mulder 28. Clinical experience with radioimmunotherapy in patients with squamous cell carcinoma of the head and neck David R. Colnot, Jasper J. Quak, Remco de Bree, Gordon B. Snow and Guus A.M.S. van Dongen 29. Immunohistological evaluation of factors related to neck metastasis in T2-4 laryngeal carcinomas Yasushi Murakami Index of authors