Klinik und Mediatorfreisetzung in der allergischen Früh- und Spätphasenreaktion

Zusammenfassung

Hintergrund: Diese Untersuchung befasst sich mit der allergischen Typ I-Spätphasenreaktion. Ziel war die Aufklärung von Zusammenhängen zwischen Nasenvolumenänderungen, klinischen Symptomen und Mediatoren der allergischen Früh- und Spätphasenreaktion. Untersucht wurden Nasensekrete auf IL-5, die Chemokine IL-8, MCP-1 und Eotaxin; das Adhäsionsmolekül sVCAM-1 sowie das Leukotrien LTC4 nach ihrem möglichen Einfluss insbesondere auf die Eosinophilie im entzündeten Gewebe.

Methoden: 13 Patienten mit saisonaler allergischer Rhinitis wurden außerhalb der Pollensaison mit ihrem spezifischen Allergen intranasal provoziert. In einem Zeitfenster von 8 h nach der Provokation beantworteten sie Symptomfragebögen und wurden mittels akustischer Rhinometrie nachuntersucht. Nasensekrete wurden fraktioniert über den Untersuchungszeitraum gewonnen und auf Gesamtprotein und die oben genannten Mediatoren untersucht.

Ergebnisse: In der Rhinometrie zeigte sich eine allergische Frühphasenreaktion in 100 % der Fälle und eine Spätphasenreaktion bei 92 %. Niesreiz und Rhinorrhoe waren die stärksten Symptome. Bei den Mediatoren konnte für IL-5, MCP-1, Eotaxin, sVCAM-1 und LTC4 eine typische Spätphasenkinetik beobachtet werden. IL-8 zeigte mit Anstiegen in der Früh- und Spätphase eine biphasische Kinetik.

Diskussion: Aus den Rhinometriewerten und den Ergebnissen der Symptome ließen sich eine deutliche Früh- und Spätphasenreaktion abbilden. Unseren Daten zufolge kommt dem TH2-Zytokin IL-5; den Chemokinen IL-8, MCP-1 und Eotaxin; sowie dem Adhäsionsmolekül sVCAM-1 und dem Leukotrien LTC4 eine relevante Rolle in der allergischen Spätphasenreaktion zu.

Abstract

Background: This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia.

Methods: 13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators.

Results: Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100 % of the cases and a late phase reaction in 92 %. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well.

Conclusions: The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.

Schlüsselwörter

Allergische Rhinitis - Spätphasenreaktion - akustische Rhinometrie - ECP - IL-5 - IL-8 - MCP-1 - Eotaxin - sVCAM-1 - LTC4

Key words

allergic rhinitis - late phase reaction - acoustic rhinometry - ECP - IL-5 - IL-8 - MCP-1 - Eotaxin - sVCAM-1 - LTC4

Literaturverzeichnis

• 1 Juniper E F. Measuring health-related quality of life in rhinitis.  J Allergy Clin Immunol. 1997;  99 S742-S749
• 2 Juniper E F, Guyatt G H. Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis.  Clin Exp Allergy. 1991;  21 77-83
• 3 Hilberg O, Jackson A C, Swift D L, Pedersen O F. Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection.  J Appl Physiol. 1989;  66 295-303
• 4 Hilberg O, Jensen F T, Pedersen O F. Nasal airway geometry: comparison between acoustic reflections and magnetic resonance scanning.  J Appl Physiol. 1993;  75 2811-2819
• 5 Raphael G D, Igarashi Y, White M V, Kaliner M A. The pathophysiology of rhinitis. V. Sources of protein in allergen-induced nasal secretions.  J Allergy Clin Immunol. 1991;  88 33-42
• 6 Kramer M F, Ostertag P, Pfrogner E, Rasp G. Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis.  Laryngoscope. 2000;  110 1056-1062
• 7 Venge P. Soluble markers of allergic inflammation.  Allergy. 1994;  49 1-8
• 8 Chihara J, Yamamoto T, Kayaba H. et al . Degranulation of eosinophils mediated by intercellular adhesion molecule-1 and its ligands is involved in adhesion molecule expression on endothelial cells-selective induction of VCAM-1.  J Allergy Clin Immunol. 1999;  103 Suppl 5 S452-S456
• 9 Greenfeder S, Umland S P, Cuss F M, Chapman R W, Egan R W. Th2 cytokines and asthma. The role of interleukin-5 in allergic eosinophilic disease.  Respir Res. 2001;  2 71-79
• 10 Bradding P, Roberts J A, Britten K M. et al . Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines.  Am J Respir Cell Mol Biol. 1994;  10 471-480
• 11 Dubucquoi S, Desreumaux P, Janin A. et al . Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion.  J Exp Med. 1994;  179 703-708
• 12 Kramer M F, Rasp G. Nasal polyposis: eosinophils and interleukin-5.  Allergy. 1999;  54 669-680
• 13 Terada N, Konno A, Natori T, Tada H, Togawa K. Interleukin-5 preferentially recruits eosinophils from vessels in nasal mucosa.  Acta Otolaryngol Suppl. 1993;  506 57-60
• 14 Ohnishi T, Sur S, Collins D S, Fish J E, Gleich G J, Peters S P. Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge.  J Allergy Clin Immunol. 1993;  92 607-615
• 15 Romagnani S. Cytokines and chemoattractants in allergic inflammation.  Mol Immunol. 2002;  38 881-885
• 16 Sallusto F, Mackay C R, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells.  Science. 1997;  277 2005-2007
• 17 Fujisawa T, Kato Y, Nagase H. et al . Chemokines induce eosinophil degranulation through CCR-3.  J Allergy Clin Immunol. 2000;  106 507-513
• 18 Braun R K, Franchini M, Erard F. et al . Human peripheral blood eosinophils produce and release interleukin-8 on stimulation with calcium ionophore.  Eur J Immunol. 1993;  23 956-960
• 19 Sehmi R, Cromwell O, Wardlaw A J, Moqbel R, Kay A B. Interleukin-8 is a chemo-attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects.  Clin Exp Allergy. 1993;  23 1027-1036
• 20 Kuna P, Lazarovich M, Kaplan A P. Chemokines in seasonal allergic rhinitis.  J Allergy Clin Immunol. 1996;  97 104-112
• 21 Garcia-Zepeda E A, Rothenberg M E, Ownbey R T, Celestin J, Leder P, Luster A D. Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia.  Nat Med. 1996;  2 449-456
• 22 Collins P D, Marleau S, Griffiths-Johnson D A, Jose P J, Williams T J. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.  J Exp Med. 1995;  182 1169-1174
• 23 Mould A W, Matthaei K I, Young I G, Foster P S. Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice.  J Clin Invest. 1997;  99 1064-1071
• 24 Ohashi Y, Nakai Y, Tanaka A. et al . Soluble vascular cell adhesion molecule-1 in perennial allergic rhinitis.  Acta Otolaryngol. 1998;  118 105-109
• 25 Bochner B S, Klunk D A, Sterbinsky S A, Coffman R L, Schleimer R P. IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells.  J Immunol. 1995;  154 799-803
• 26 Henderson W RJ, Lewis D B, Albert R K. et al . The importance of leukotrienes in airway inflammation in a mouse model of asthma.  J Exp Med. 1996;  184 1483-1494
• 27 Marom Z, Shelhamer J H, Bach M K, Morton D R, Kaliner M. Slow-reacting substances, leukotrienes C4 and D4, increase the release of mucus from human airways in vitro.  Am Rev Respir Dis. 1982;  126 449-451
• 28 Rasp G. Akustische Rhinometrie: Messung der Früh- und Spätphase der allergischen Sofortreaktion bei der allergischen Rhinitis.  Laryngorhinootologie. 1993;  72 125-130
• 29 Zweiman B, Getsy J, Kalenian M. et al . Nasal airway changes assessed by acoustic rhinometry and mediator release during immediate and late reactions to allergen challenge.  J Allergy Clin Immunol. 1997;  100 624-631
• 30 Klimek L, Rasp G. Norm values for eosinophil cationic protein in nasal secretions: influence of specimen collection.  Clin Exp Allergy. 1999;  29 367-374
• 31 Kramer M F, Burow G, Pfrogner E, Rasp G. In vitro diagnosis of chronic nasal inflammation.  Clin Exp Allergy. 2004;  34 1086-1092
• 32 Bachert C, Behrendt H, Diepgen T, Fuchs T. Weißbuch - Allergie in Deutschland 2000. München; Urban und Vogel Medien- und Medizin-Verl.-Ges 2000
• 33 Iliopoulos O, Proud D, Adkinson N F, Norman P S, Kagey-Sobotka A, Lichtenstein L M. Relationship between the early and late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells.  J Allergy Clin Immunol. 1990;  86 851-861
• 34 Lebel B, Bousquet J, Morel A, Chanal I, Godard P, Michel F B. Correlation between the symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains.  J Allergy Clin Immunol. 1988;  82 869-877
• 35 Pelikan Z. Late and delayed responses of the nasal mucosa to allergen challenge.  Ann Allergy. 1978;  41 37-47
• 36 Wang D, Clement P. Assessment of early- and late-phase nasal obstruction in atopic patients after nasal allergen challenge.  Clin Otolaryngol. 1995;  20 368-373
• 37 Eccles R, Reilly M, Eccles K S. Changes in the amplitude of the nasal cycle associated with symptoms of acute upper respiratory tract infection.  Acta Otolaryngol. 1996;  116 77-81
• 38 Lund V J. Nasal physiology: neurochemical receptors, nasal cycle, and ciliary action.  Allergy Asthma Proc. 1996;  17 179-184
• 39 Simon H U, Yousefi S, Weber M. et al . Human peripheral blood eosinophils express and release interleukin-8.  Int Arch Allergy Immunol. 1995;  107 124-126
• 40 Howarth P H. Leukotrienes in rhinitis.  Am J Respir Crit Care Med. 2000;  161 S133-S136
• 41 Moller A, Lippert U, Lessmann D. et al . Human mast cells produce IL-8.  J Immunol. 1993;  151 261-3266
• 42 Christodoulopoulos P, Wright E, Frenkiel S, Luster A, Hamid Q. Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: effect of topical corticosteroids.  J Allergy Clin Immunol. 1999;  103 1036-1044
• 43 Gu L, Tseng S, Horner R M, Tam C, Loda M, Rollins B J. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1.  Nature. 2000;  404 407-411
• 44 Humbles A A, Conroy D M, Marleau S. et al . Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo.  J Exp Med. 1997;  186 601-612
• 45 Yamada H, Yamaguchi M, Yamamoto K. et al . Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum.  Allergy. 2000;  55 392-397
• 46 Baraniuk J N. Pathogenesis of allergic rhinitis.  J Allergy Clin Immunol. 1997;  99 Suppl 2 S763-S772
• 47 Drazen J M, Austen K F, Lewis R A. et al . Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro.  Proc Natl Acad Sci USA. 1980;  77 4354-4358
• 48 Underwood D C, Osborn R R, Newsholme S J, Torphy T J, Hay D W. Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig: modulation by the LTD4 receptor antagonist, pranlukast, or an interleukin-5 monoclonal antibody.  Am J Respir Crit Care Med. 1996;  154 850-857
• 49 Ellis J L, Undem B J. Role of peptidoleukotrienes in capsaicin-sensitive sensory fibre-mediated responses in guinea-pig airways.  J Physiol. 1991;  436 469-484
• 50 McAlexander M A, Myers A C, Undem B J. Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction of guinea pig isolated airway.  J Pharmacol Exp Ther. 1998;  285 602-607