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DESCRIPTION
OVERVIEW
The Symposium is being held under the auspices of the International Eosinophil Society. The meeting will host ~35 invited featured
speakers, and 24 additional oral talks (10 min + 5 min discussion) and ~50 posters which will be selected from submitted abstracts of junior scientists (graduate students, postdoctoral fellows, junior
faculty). More than 200 participants are anticipated who will have the opportunity to submit abstracts for selection for oral or poster presentations. A cutting edge program of basic,
translational, and clinical research is being prepared by members of the Organizing and Program Committees and its International Scientific Advisory Board. The conference provides an outstanding
opportunity for presentations and breakout sessions on the most recent advances in this biomedically important,diverse and rapidly advancing field. The meeting consists of invited talks by leaders
in eosinophil research and allied fields from the perspectives of asthma, allergy, gastrointestinal, hematologic, neoplastic, fibrotic, and tropical/parasitic diseases. The focus will be on basic
aspects of eosinophil cellular, molecular and immunobiology, and clinical issues relevant to the functions of eosinophils in both normal physiology, inflammation and disease pathogenesis.
Opportunities are included for breakout sessions on applications of eosinophil biology to drug discovery and therapeutics for eosinophil-associated diseases. The meeting format provides a highly
interactive, workshop-like forum for both the plenary talks, and the oral and poster presentations of submitted abstracts, especially by younger scientists (graduate students, postdoctoral
fellows). The symposium covers the following major themes: (1) Eosinophil development, maturation, recruitment and migration, priming and activation, and death, (2) Normal versus pathophysiologic
roles of eosinophils in asthma, allergy, tropical diseases, tissue remodeling and fibrosis, EMS, HES, eosinophil leukemia and cancer biology, (3) Current issues in the clinical evaluation/treatment of
eosinophil-associated diseases and syndromes, (4) Unanswered questions and future directions in eosinophil research. The symposium will accomplish the following goals: (1) Provide a venue for
bringing together basic and clinical scientists addressing eosinophil biology at different organizational levels and in animal models to foster understanding of their roles in normal versus
pathophysiologic conditions, (2) Bring together basic and clinical investigators to foster the development of clinical therapeutics, diagnostic tests and other treatments of eosinophil-associated
diseases based on understanding eosinophil immunobiology and inflammatory functions, (3) Provide participants with the latest information on eosinophil basic and clincial research by including many short
talks from submitted abstracts, (4) Provide all participants with opportunities for in-depth discussions and exchange of ideas with speakers and poster presenters for cross-fertilization and
establishment of collaborations between basic and clinical disciplines, and (5) Provide an interactive forum for effective scientific exchange amongst senior and promising junior scientists and
minorities working in the fields of allergy, immunology, tropical diseases, hematology, and cancer research in terms of the functions of eosinophils in normal physiology in health and pathophysiology in
disease.
CONFERENCE PLAN [top]
This conference will be the third biennial gathering of basic and clincial scientists from around the world focused exclusively on the
eosinophilic granulocyte, specifically its cell biology, immunobiology, biochemistry, molecular biology, and pathobiology in eosinophil-associated diseases such as asthma, allergic, parasitic,
gastrointestinal and neoplastic diseases, as well as idiopathic syndromes such as the hypereosinophilic syndrome and eosinophil myalgia syndrome. The previous two meetings were held in Lund Sweden in
1999, and Banff Alberta, Canada in 2001. The first meeting included the initial establishment of the International Eosinophil Society, which now serves as the international sponsor of these meetings. The
present, 3rd, meeting will again be held under the auspices of the International Eosinophil Society, with sponsorship, organizational and administrative oversight by the University of Illinois
at Chicago. The meeting will host 35-40 invited Faculty speakers. We anticipate more than 200 participants who will have the opportunity to submit abstracts for selection for oral or poster
presentations, and pay a registration fee. The meeting will begin with a reception on Wednesday, June 25 and finish at noon on Sunday, June 29 for a full 3.5 days of scientific sessions. A
state-of-the-art, cutting edge program of basic, translational, and clinical research is being prepared by members of the Symposium’s Organizing Committee and its International Advisory Board, and the
Executive and Program Committees of the International Eosinophil Society.
The Symposium will provide an outstanding opportunity for up-to-date presentations and breakout sessions on the most recent advances in
this biomedically important and diverse field. The Conference will consist of plenary presentations by various leaders in eosinophil research and allied fields from the perspectives of asthma,
allergy, gastrointestinal and parasitic diseases. The focus will be on basic aspects of eosinophil cellular, molecular and immunobiology, including translational and clinical issues relevant to the
roles of eosinophils in both normal physiology and disease pathogenesis. The symposium will also include opportunities for discussions on the application of eosinophil biology to drug discovery in
biomedicine. The symposium format will provide a highly interactive, workshop-like forum for both oral and poster presentations of submitted abstracts, especially by younger scientists,
postdoctoral and graduate student trainees. The provisional program for the symposium covers the following major themes:
- Eosinophil growth, differentiation, gene transcription, expression and regulation, survival, death
- Eosinophil receptors, signaling, priming, adhesion, activation and mediator secretion
- Eosinophils among inflammatory and stromal cells – functional interactions and contrasts
- Animal models of eosinophil roles and functions in asthma, allergy, parasitic and gastrointestinal diseases, and viral infections
- Clinical aspects and issues in eosinophil function in asthma, allergy, other eosinophil-associated diseases, tissue pathology,
remodeling and fibrosis
- New therapeutics, basic and clinical research strategies, and future directions
- Meeting summary
PRE-SYMPOSIUM CLINICAL WORKSHOP [top]
There will be a pre-conference clinical workshop on June 24-25 at the Snowmass, Aspen venue on the development of diagnostic and
treatment criteria for patients with hypereosinophilic syndromes. This meeting is sponsored by the NIH Office of Rare Diseases and is being organized by Dr. Amy Klion from the National Institute of
Allergy and Infectious Diseases. The workshop will have approximately 35 participants, many of whom will also participate in the International Eosinophil Symposium.
By combining both basic scientists and clinician-investigators doing translational and applied research on asthma, allergy and other
eosinophil-asssociated diseases, the symposium is expected to accomplish the following goals:
- To provide an outstanding venue for bringing together basic scientists addressing eosinophil cellular, molecular and immunobiology
at different organizational levels (e.g. in vitro cell biology, biochemistry, molecular biology and pharmacology versus in vivo immunobiology, pharmacology and physiology in animal models of disease and human clinical studies) to better understand the interrelationships between basic eosinophil biology and the roles of eosinophils in both normal host physiology and the pathophysiology of eosinophil-associated diseases.
- To bring together basic scientists and clinical investigators to better identify and understand the roles of eosinophils in normal
physiology versus disease pathology for the purpose of fostering the development of new therapeutics, diagnostic tests and treatments that are based on sound basic science and a full understanding of
eosinophil biology and functions in vivo.
- To provide meeting participants with the latest available information on basic aspects of the cell and molecular biology, and
immunobiology of the eosinophil, and the roles of the eosinophil in normal versus pathophysiologic processes in health and disease, by including both “state-of-the-art” plenary presentations from
leading labs, as well as many short presentations selected from submitted abstracts.
- To provide all meeting participants with multiple opportunities for in-depth discussion with invited speakers, poster presenters,
towards the all-important goals of enabling cross-fertilization between basic and translational/applied aspects of eosinophil biology and the encouragement and establishment of collaborative research
projects.
- To provide an opportunity and outstanding forum for promising junior scientists (graduate students, postdoctoral trainees and
junior faculty), female scientists, and underrepresented minorities to present their research and play a major role in the conduct and success of the meeting.
- To provide a forum for reviewing current understanding and new approaches in the clinical evaluation and treatment of
eosinophil-associated diseases, and importantly to identify current issues, unanswered questions and future directions for eosinophil research.
TIMELINESS AND NEED FOR THE SYMPOSIUM [top]
The need for the 3rd International Eosinophil Symposium is based on a number of key factors, not the least of which are the current
controversies and very new findings regarding the roles of the eosinophil in asthma, including inflammation, airways hyperreactivity, tissue remodeling and subepithelial fibrosis1. Recent clinical studies using anti-IL-5 monoclonal
antibodies have opened new insights towards a clearer understanding of the functions of this unique granulocyte in health and disease pathophysiology. In addition, since the last (2nd)
International Eosinophil Sympoisum in Banff, Canada, there has been significant increase in the numbers of publications in the eosinophil field, as well as new discoveries related to the intracellular
mechanisms involved in eosinophil recruitment to tissues2, long-term tissue survival, and eosinophil secretory processes in vivo that are all highly relevant clinically to both the roles and functions of the eosinophil in asthma, allergic tissue responses such as late phase reactions, tissue remodeling and fibrosis in eosinophil-associated disease pathophysiology3-5. As well, new insights into the roles of the
eosinophil in the normal and pathophysiology of the gastrointestinal tract have emerged from recent studies in both animal models as well as clincial studies of eosinophil-associated gastrointestinal
diseases6-9. These new studies are
at the forefront of the development of novel therapeutic strategies that specifically target eosinophil migration and activation by key eosinophil-active cytokines and chemokines10,11; these factors are involved in eosinophil priming,
recruitment, activation, survival and secretion of protein and lipid mediators that impact directly on tissues in terms of both inflammatory damage as well as the activation of fibroblasts and
induction of myofibroblast differentiation that disrupts extracellular matrix homeostasis leading to tissue fibrosis. As well, new insights in the active roles of the eosinophil in interacting with
and modulating T cells responses in allergic diseases is beginning to emerge6,12, novel interactions with parasympathetic neurons and production of nerve growth factor that may have significant implications for the roles of
eosinophils in asthma13-16,as are recent
stunning successes in treating the hypereosinophilic syndrome and chronic eosinophil leukemias with new kinase inhibitors developed for chronic myelogenous leukemia17,18. The 2nd International Eosinophil Symposium, a highly
successful gathering of scientists at both the basic and clincal levels, provided unique opportunities for the establishment of collaborative investigations in these areas that are already bearing fruit
in terms recent publications, new cutting edge approaches to address key questions, issues and controversies in the areas of asthma and related allergic diseases. The time is thus ripe for the 3rd
International Eosinophil Symposium, a meeting which is vitally important to foster this new understanding and momentum, and importantly to ensure that the next generation of junior scientists and
clinicians interested in asthma, allergic and related diseases research will be exposed to state-of-the-art advances in this diverse and rapidly developing field.
The first International Eosinophil Symposium in Lund, Sweden was initially conceived and organized by Professor Per Venge, current
President of the International Eosinophil Society, and his colleagues after recognizing: (1) that eosinophil research had grown exponentially during the past 15-20 years and had begun to have a
significant impact on understanding the pathophysiology and treatment of allergic diseases such as asthma, (2) that the field included well over 300 researchers, and (3) that eosinophil research,
although occasionally covered in individual talks and specific sessions of more broadly planned meetings such recent Keystone Symposia, and the annual meetings of the American Association of Allergy,
Asthma and Immunology, American Thoracic Society, American Association of Immunologists, and their European and other counterparts, lacked a national or international forum focused exclusively on the
basic and clinical aspects of eosinophil biology. Importantly, it was recognized that this field would benefit significantly and be moved forward more rapidly by establishing a biennial meeting for
bringing basic and clinical eosinophil biologists together to foster collaborative translational science and clinical studies linking the “bench to the bedside”. As with the present planned meeting,
there was an appreciation of the need to bring basic and clinical researchers together to understand the relationships between eosinophil structure and function and disease pathophysiology and treatment,
although at that time, the meeting was somewhat more skewed towards basic eosinophil science, since this reflected the state-of-the-art in 1999. In addition to resulting in the birth of the
International Eosinophil Society, the 1999 meeting was considered so successful by the 150+ participants, that a second meeting was conceived by the nascent executive committee and organized by Professor
Redwan Moqbel and colleagues for 2001 in Banff, Alberta, Canada for the purpose both of honoring five of the major contributors to the growth and successes of the eosinophil field over the past 20 years,
as well as establishing a biennial meeting to foster international scientific exchange in the new millennium as clinical trials of eosinophil-based therapeutics began to test hypotheses of eosinophil
disease associations and lend new insights into the roles of eosinophils in inflammation and the pathophysiology of asthma and other allergic diseases.
Indeed, the first clinical trials using anti-IL-5 monoclonal antibody (mepolizumab) in asthmatic subjects suggested that elimination of
eosinophils from the airway lumen and blood does not impact on airway hyperreactivity or function19. However, this study was found to be seriously flawed in its design and interpretation by a number of investigators, since it lacked both
statistical power20 and most importantly, a rigorous demonstration that eosinophils had been completely eliminated from key sights in the lung where eosinophils are thought to directly impact lung function, e.g. in the regions beneath the lamina reticularis, perivascular locations and parasympathetic neuronal tissue10. Publication of this report sparked serious and at
times heated debate and discussions at scientific meetings such as the annual meeting of the American Academy of Asthma, Allergy and Immunology, American Thoracic Society, European Thoracic Society, the
2nd International Eosinophil Symposium1 and others, as well as sparked a series of scholarly letters and reviews of the Leckie et al study, soundly criticizing the study as seriously flawed1,10,20. Nevertheless, the eosinophil research field
took a serious hit that negatively impacted eosinophil researchers in the United States and around the world, resulting in problems from renewing grants and loss of funding for some investigators, to
reorganization of some eosinophil-related research and development programs in the pharmaceutical industry. Most importantly, a number of follow-up studies of anti-IL-5 clinical trials in asthma
and other diseases have indicated that the anti-IL-5 antibody fails to completely eliminate eosinophils from key sites in affected pulmonary tissues in the asthmatic lung and bone marrow 1. These findings, reported last year in a
late-breaking abstract session in New York at the AAAAI meeting21 and recently published22, clearly indicated that other, non-IL-5 mediated mechanisms maintain eosinophils in key pulmonary tissue localizations for long periods of
time. As well, recent findings have indicated that both eotaxins and IL-5 will need to be targeted to completely block eosinophil migration and retention (survival) in pulmonary and other tissues
such as the GI tract, implicating a clear role for the eotaxin receptor in eosinophil recruitment6,23-25. Moreover, in recent highly pertinent clinical studies of anti-IL-5 antibody performed by Patrick Flood-Page and colleagues in the
laboratories of Professor A.B.Kay and Douglas Robinson in the UK, these investigators show that intravenous administration anti-IL-5 (mepolizumab) antibody to mild atopic asthmatics significantly reduces
the expression of extracellular matrix proteins that contribute to subepithelial fibrosis in the asthmatic lung, including tenascin, procollagen III and lumican in the bronchial mucosal reticular
basement membrane, providing compelling evidence for a role for eosinophils in airways remodelling in asthma26. As well, this group has now demonstrated significant effects of intravenous administration of an anti-IL-5 monoclonal antibody
(mepolizumab) on allergen-induced tissue eosinophilia, the late-phase allergic reaction and the expression of markers of repair/remodelling in human atopic subjects 27. The magnitude of the
allergen-induced late phase reaction (as a model of chronic allergic inflammation) and the numbers of tenascin-positive cells (as a marker of repair/remodeling) was evaluated in atopic allergic subjects
before and after the intravenous administration of the anti-IL-5 monoclonal antibody (mepolizumab). Anti-IL-5 significantly inhibited eosinophil infiltration at both 6 hrs and 48 hrs in skin biopsies, as
well as the numbers of tenascin immunoreactive cells at 48 hr. However, there was no effect, at either time point, on the size of the late phase cutaneous allergic reaction. These investigators conclude
that eosinophils play a role in repair/remodeling processes associated with allergic inflammation, but are unlikely to cause the redness, swelling and induration which characterizes the late phase
allergic response in the skin3,27, which
is more likely due to mast cell and/or basophil activation as the initiating stimulus. These studies are breathing considerable renewed vitality, interest and insights into the eosinophil field, and
speak to the timeliness of bringing eosinophil researchers together again for an International meeting in 2003 to discuss these issues, new questions and future directions that the field should take1. Thus, rather than being down and out for the count,
our theme for this next Symposium is “Eosinophil Rising 2003”!
LITERATURE CITED [top]
1. Lacy P, Weller PF, Moqbel R. A report from the International Eosinophil Society: eosinophils in a tug of war. J Allergy Clin Immunol. 2001;108:895-900
2. Adamko D, Lacy P, Moqbel R. “Mechanisms of eosinophil recruitment and activation.” Curr Allergy Asthma Rep. 2002;2:107-116
3. Phipps S, Ying S, Wangoo A, Ong Y-E, Levi-Schaffer F, Kay AB. “The relationship between allergen-induced tissue eosinophilia
and markers of repair and remodeling in human atopic skin.” J. Immunol. 2002;169:4604-4612
4. Phipps S, Flood-Page P, Menzies-Gow A, Ong Y-E, Kay AB. “Effect of intravenous administration of an anti-IL-5 monoclonal
antibody (mepolizumab) on allergen-induced tissue eosinophilia, the late-phase allergic reaction and the expression of a marker of repair/remodelling in human atopic subjects.” J. Immunol. 2002;Submitted
5. Phipps S, Kay BA. “Eosinophil-induced myofibroblast differentiation.” Journal of Allergy and Clinical Immunology. 2001;107:S323
6. Mattes J, Yang M, Mahalingam S, Kuehr J, Webb DC, Simson L, Hogan SP, Koskinen A, McKenzie AN, Dent LA, Rothenberg ME, Matthaei
KI, Young IG, Foster PS. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in
experimental asthma. J Exp Med. 2002;195:1433-1444
7. Hogan SP, Foster PS, Rothenberg ME. “Experimental analysis of eosinophil-associated gastrointestinal diseases.” Curr Opin Allergy Clin Immunol. 2002;2:239-248
8. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. “IL-5 promotes eosinophil trafficking to the esophagus.” J Immunol. 2002;168:2464-2469
9. Furuta GT. “More than food trafficks into the esophagus.” Gastroenterology. 2002;123:946-947
10. Foster PS, Hogan SP, Yang M, Mattes J, Young IG, Matthaei KI, Kumar RK, Mahalingam S, Webb DC. “Interleukin-5 and
eosinophils as therapeutic targets for asthma.” Trends Mol Med. 2002;8:162-167
11. Foster PS, Martinez-Moczygemba M, Huston DP, Corry DB. “Interleukins-4, -5, and -13: emerging therapeutic targets in
allergic disease.” Pharmacol Ther. 2002;94:253-264
12. Shi HZ, Humbles A, Gerard C, Jin Z, Weller PF. “Lymph node trafficking and antigen presentation by endobronchial
eosinophils.” J Clin Invest. 2000;105:945-953
13. Costello RW, Jacoby DB, Gleich GJ, Fryer AD. “Eosinophils and airway nerves in asthma.” Histol Histopathol. 2000;15:861-868
14. Jacoby DB, Costello RM, Fryer AD. “Eosinophil recruitment to the airway nerves.” J Allergy Clin Immunol. 2001;107:211-218
15. Sawatzky DA, Kingham PJ, Court E, Kumaravel B, Fryer AD, Jacoby DB, McLean WG, Costello RW. “Eosinophil adhesion to
cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation.” Am J Physiol Lung Cell Mol Physiol. 2002;282:L1279-1288
16. Kobayashi H, Gleich GJ, Butterfield JH, Kita H. “Human eosinophils produce neurotrophins and secrete nerve growth
factor on immunologic stimuli.” Blood. 2002;99:2214-2220
17. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. “Treatment of hypereosinophilic syndrome with
imatinib mesilate.” Lancet. 2002;359:1577-1578
18. Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE,
Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM. “Response to imatinib mesylate in patients with chronic myeloproliferative diseases with
rearrangements of the platelet-derived growth factor receptor beta.” N Engl J Med. 2002;347:481-487
19. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel
TT, Holgate ST, Sterk PJ, Barnes PJ. “Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response.” Lancet. 2000;356:2144-2148
20. O'Byrne PM, Inman MD, Parameswaran K. “The trials and tribulations of IL-5, eosinophils, and allergic asthma.” J Allergy Clin Immunol. 2001;108:503-508
21. Flood-Page P, Menzies-Gow A, Compton C, Walls C, Barnes N, Robinson D, Kay AB. "Late Breaking Abstract": Does
anti-IL-5 deplete bronchial mucosal eosinophils in mild atopic asthma? J Allergy Clin Immunol. 2002;190:2801
22. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. “Eosinophil's Role Remains Uncertain as Anti-Interleukin-5 only
Partially Depletes Numbers in Asthmatic Airway.” Am J Respir Crit Care Med. 2003;167:199-204
23. Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, Friend DS, Oettgen HC, Gerard C, Geha RS. “CCR3 is
essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation.” J Clin Invest. 2002;109:621-628
24. Humbles AA, Lu B, Friend DS, Okinaga S, Lora J, Al-Garawi A, Martin TR, Gerard NP, Gerard C. “The murine CCR3
receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness.” Proc Natl Acad Sci U S A. 2002;99:1479-1484
25. Gurish MF, Humbles A, Tao H, Finkelstein S, Boyce JA, Gerard C, Friend DS, Austen KF. “CCR3 is required for tissue
eosinophilia and larval cytotoxicity after infection with Trichinella spiralis.” J Immunol. 2002;168:5730-5736
26. Flood-Page P, Menzies-Gow A, Wangoo A, Barnes N, Akans JB, Robinson D, Kay AB. “Intravenous administration anti-IL-5
(mepolizumab) to mild atopic asthmatics reduces the expression of tenascin, procollagen III and lumican in the bronchial mucosal reticular basement membrane: evidence for a role for eosinophils in
airways remodelling.” Submitted. 2002
27. Phipps S, Ying S, Wangoo A, Ong YE, Levi-Schaffer F, Kay AB. “The relationship between allergen-induced tissue
eosinophilia and markers of repair and remodeling in human atopic skin.” J Immunol. 2002;169:4604-4612
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