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Антигистаминные, противовоспалительные и противоаллергические свойства дезлоратадина
Антигистаминные, противовоспалительные и противоаллергические свойства дезлоратадина
Ильина Н.И., Павлова К.С. Антигистаминные, противовоспалительные и противоаллергические свойства дезлоратадина. Consilium Medicum. 2015; 3: 79–83.
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Аннотация
Гистамин является одним из наиболее важных медиаторов, который высвобождается из тучных клеток и базофилов при аллергической патологии. Основными средствами для лечения аллергии являются Н1-антигистаминные препараты II поколения (АГ II), которые представляют собой высокоспецифичные агонисты Н1-рецепторов длительного действия. Исследования последних лет показали, что некоторые АГ II помимо антигистаминной активности имеют противовоспалительную активность, не связанную с блокадой Н1-рецепторов, а обусловленную блокированием высвобождения медиаторов воспаления базофилами, тучными клетками, уменьшением экспрессии молекул адгезии и угнетением привлечения в зону воспаления клеток аллергического ответа. Таким образом, антигистаминные препараты II поколения могут подавлять развитие поздней фазы и предотвращать хронизацию аллергического воспаления. Данная статья представляет собой обзор имеющейся на данный момент информации по антигистаминному, противовоспалительному и противоаллергическому профилю дезлоратадина.
Ключевые слова: аллергический ринит, антигистаминные препараты, противовоспалительный эффект, дезлоратадин, Эриус, антигистаминные препараты II поколения, крапивница.
Key words: allergic rhinitis, antihistamines, anti-inflammatory effect, desloratadine, Erius, antihistamines second generation, urticaria.
Ключевые слова: аллергический ринит, антигистаминные препараты, противовоспалительный эффект, дезлоратадин, Эриус, антигистаминные препараты II поколения, крапивница.
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Key words: allergic rhinitis, antihistamines, anti-inflammatory effect, desloratadine, Erius, antihistamines second generation, urticaria.
Полный текст
Список литературы
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2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
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14. Costa T, Cotecchia S. Historical review: negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol Sci 2005; 26: 618–24.
15. De Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G-protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1–12.
16. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H1 receptor antagonists. Eur J Pharmacol 2000; 387: R5–R7.
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24. Siebenhaar F, Degener F, Zuberbier T et al. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009; 123: 672–9.
25. Zuberbier T, Canonica GW. Desloratadine significantly decreases total symptoms scores in subjects with persistent allergic rhinitis: ACCEPT-2 study in collaboration with GA2LEN. Ann Allergy Asthma Immunol 2009; 102: A119.
26. Anthes JC, Gilchrest H, Richard C Eckel S et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor. Eur J Pharmacol 2002; 449: 229–37.
27. Wu R-L, Anthes JC, Kreutner W et al. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-кB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 2004; 135: 313–8.
28. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006; 24: 147–74.
29. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (Suppl.): S460–S475.
30. Lebel B, Bousquet J, Czarlewski W, Campbell AM. Loratadine (L) reduces RANTES release by an epithelial cell line. J Allergy Clin Immunol 1997; 99: S444. Abstract 1802.
31. Kowalski ML, Lewandowska A, Wozniak J et al. Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine. Allergy 2005; 60: 80–5.
32. Wang YH, Taché Y, Harris AG et al. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique. Allergy 2005; 60: 117–24.
33. Genovese A, Patella V, De Crescenzo G et al. Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRl+ cells. Clin Exp Allergy 1997; 27: 559–67.
34. Lippert U, Kru¨ger-Krasagakes S, Mo¨ller A et al. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines. Exp Dermatol 1995; 4 (Part. 2): 272–6.
35. Weller K, Maurer M. Desloratadine inhibits human skin mast cell activation and histamine release. J Invest Dermatol 2009; 129: 2723–6.
36. Molet S, Gosset P, Lassalle P et al. Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells. Clin Exp Allergy 1997; 27: 1167–74.
37. Vignola AM, Crampette L, Mondain M et al. Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells. Allergy 1995; 50: 200–3.
38. Traidl-Hoffmann C, Mu¨nster I, Ring J, Behrendt H. Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: implications for anti-inflammatory activity of antihistamines. Int Arch Allergy Immunol 2006; 140: 315–20.
2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
3. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 2002; 23: 255–63.
4. Baena-Cagnani CE. Desloratadine activity in concurrent seasonal allergic rhinitis and asthma. Allergy 2001; 56: 21–7.
5. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1418–26.
6. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7: 41–53.
7. Das AK, Yoshimura S, Mishima R et al. Stimulation of histamine H1 receptor up-regulates histamine H1-receptor itself through activation of receptor gene transcription. J Pharmacol Sci 2007; 103: 374–82.
8. Simons FER. Advances in H1-antihistamines. N Engl J Med 2004; 351: 2203–17.
9. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133–42.
10. Canonica GW, Blaiss M. Antihistaminic, anti-Inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. WAO Journal 2011; 4: 47–53.
11. Greasley PJ, Clapham JC. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 2006; 553: 1–9.
12. Scadding G. Predicting and establishing the clinical efficacy of a histamine H1- receptor antagonist: desloratadine, the model paradigm. Clin Drug Invest 2005; 25: 153–64.
13. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32: 489–98.
14. Costa T, Cotecchia S. Historical review: negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol Sci 2005; 26: 618–24.
15. De Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G-protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1–12.
16. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H1 receptor antagonists. Eur J Pharmacol 2000; 387: R5–R7.
17. Bousquet J, Khaltaev N, Cruz AA et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008; 63 (Suppl. 86): 8–160.
18. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64: 1427–43.
19. Bousquet J, Bachert C, Canonica GW et al. ACCEPT-1 Study Group. Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study. Allergy 2009; 64: 1516–23.
20. Canonica GW, Tarantini F, Compalati E, Penagos M. Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials. Allergy 2007; 62: 359–66.
21. Monroe E, Finn A, Patel P et al. Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomised, placebo-controlled trial. J Am Acad Dermatol 2003; 48: 535–41.
22. Ortonne J-P, Grob J-J, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8: 37–42.
23. Ring J, Hein R, Gauger A et al. Desloratadine Study Group. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Int J Dermatol 2001; 40: 72–6.
24. Siebenhaar F, Degener F, Zuberbier T et al. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009; 123: 672–9.
25. Zuberbier T, Canonica GW. Desloratadine significantly decreases total symptoms scores in subjects with persistent allergic rhinitis: ACCEPT-2 study in collaboration with GA2LEN. Ann Allergy Asthma Immunol 2009; 102: A119.
26. Anthes JC, Gilchrest H, Richard C Eckel S et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor. Eur J Pharmacol 2002; 449: 229–37.
27. Wu R-L, Anthes JC, Kreutner W et al. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-кB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 2004; 135: 313–8.
28. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006; 24: 147–74.
29. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (Suppl.): S460–S475.
30. Lebel B, Bousquet J, Czarlewski W, Campbell AM. Loratadine (L) reduces RANTES release by an epithelial cell line. J Allergy Clin Immunol 1997; 99: S444. Abstract 1802.
31. Kowalski ML, Lewandowska A, Wozniak J et al. Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine. Allergy 2005; 60: 80–5.
32. Wang YH, Taché Y, Harris AG et al. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique. Allergy 2005; 60: 117–24.
33. Genovese A, Patella V, De Crescenzo G et al. Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRl+ cells. Clin Exp Allergy 1997; 27: 559–67.
34. Lippert U, Kru¨ger-Krasagakes S, Mo¨ller A et al. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines. Exp Dermatol 1995; 4 (Part. 2): 272–6.
35. Weller K, Maurer M. Desloratadine inhibits human skin mast cell activation and histamine release. J Invest Dermatol 2009; 129: 2723–6.
36. Molet S, Gosset P, Lassalle P et al. Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells. Clin Exp Allergy 1997; 27: 1167–74.
37. Vignola AM, Crampette L, Mondain M et al. Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells. Allergy 1995; 50: 200–3.
38. Traidl-Hoffmann C, Mu¨nster I, Ring J, Behrendt H. Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: implications for anti-inflammatory activity of antihistamines. Int Arch Allergy Immunol 2006; 140: 315–20.
2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
3. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 2002; 23: 255–63.
4. Baena-Cagnani CE. Desloratadine activity in concurrent seasonal allergic rhinitis and asthma. Allergy 2001; 56: 21–7.
5. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1418–26.
6. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7: 41–53.
7. Das AK, Yoshimura S, Mishima R et al. Stimulation of histamine H1 receptor up-regulates histamine H1-receptor itself through activation of receptor gene transcription. J Pharmacol Sci 2007; 103: 374–82.
8. Simons FER. Advances in H1-antihistamines. N Engl J Med 2004; 351: 2203–17.
9. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133–42.
10. Canonica GW, Blaiss M. Antihistaminic, anti-Inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. WAO Journal 2011; 4: 47–53.
11. Greasley PJ, Clapham JC. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 2006; 553: 1–9.
12. Scadding G. Predicting and establishing the clinical efficacy of a histamine H1- receptor antagonist: desloratadine, the model paradigm. Clin Drug Invest 2005; 25: 153–64.
13. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32: 489–98.
14. Costa T, Cotecchia S. Historical review: negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol Sci 2005; 26: 618–24.
15. De Ligt RA, Kourounakis AP, IJzerman AP. Inverse agonism at G-protein-coupled receptors: (patho) physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1–12.
16. Bakker RA, Wieland K, Timmerman H, Leurs R. Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H1 receptor antagonists. Eur J Pharmacol 2000; 387: R5–R7.
17. Bousquet J, Khaltaev N, Cruz AA et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008; 63 (Suppl. 86): 8–160.
18. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64: 1427–43.
19. Bousquet J, Bachert C, Canonica GW et al. ACCEPT-1 Study Group. Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study. Allergy 2009; 64: 1516–23.
20. Canonica GW, Tarantini F, Compalati E, Penagos M. Efficacy of desloratadine in the treatment of allergic rhinitis: a meta-analysis of randomized, double-blind, controlled trials. Allergy 2007; 62: 359–66.
21. Monroe E, Finn A, Patel P et al. Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomised, placebo-controlled trial. J Am Acad Dermatol 2003; 48: 535–41.
22. Ortonne J-P, Grob J-J, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8: 37–42.
23. Ring J, Hein R, Gauger A et al. Desloratadine Study Group. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Int J Dermatol 2001; 40: 72–6.
24. Siebenhaar F, Degener F, Zuberbier T et al. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol 2009; 123: 672–9.
25. Zuberbier T, Canonica GW. Desloratadine significantly decreases total symptoms scores in subjects with persistent allergic rhinitis: ACCEPT-2 study in collaboration with GA2LEN. Ann Allergy Asthma Immunol 2009; 102: A119.
26. Anthes JC, Gilchrest H, Richard C Eckel S et al. Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor. Eur J Pharmacol 2002; 449: 229–37.
27. Wu R-L, Anthes JC, Kreutner W et al. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-кB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 2004; 135: 313–8.
28. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006; 24: 147–74.
29. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111 (Suppl.): S460–S475.
30. Lebel B, Bousquet J, Czarlewski W, Campbell AM. Loratadine (L) reduces RANTES release by an epithelial cell line. J Allergy Clin Immunol 1997; 99: S444. Abstract 1802.
31. Kowalski ML, Lewandowska A, Wozniak J et al. Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine. Allergy 2005; 60: 80–5.
32. Wang YH, Taché Y, Harris AG et al. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique. Allergy 2005; 60: 117–24.
33. Genovese A, Patella V, De Crescenzo G et al. Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FceRl+ cells. Clin Exp Allergy 1997; 27: 559–67.
34. Lippert U, Kru¨ger-Krasagakes S, Mo¨ller A et al. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines. Exp Dermatol 1995; 4 (Part. 2): 272–6.
35. Weller K, Maurer M. Desloratadine inhibits human skin mast cell activation and histamine release. J Invest Dermatol 2009; 129: 2723–6.
36. Molet S, Gosset P, Lassalle P et al. Inhibitory activity of loratadine and descarboxyethoxyloratadine on histamine-induced activation of endothelial cells. Clin Exp Allergy 1997; 27: 1167–74.
37. Vignola AM, Crampette L, Mondain M et al. Inhibitory activity of loratadine and descarboethoxyloratadine on expression of ICAM-1 and HLA-DR by nasal epithelial cells. Allergy 1995; 50: 200–3.
38. Traidl-Hoffmann C, Mu¨nster I, Ring J, Behrendt H. Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: implications for anti-inflammatory activity of antihistamines. Int Arch Allergy Immunol 2006; 140: 315–20.
________________________________________________
2. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy 2008; 94: 67–82.
3. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol 2002; 23: 255–63.
4. Baena-Cagnani CE. Desloratadine activity in concurrent seasonal allergic rhinitis and asthma. Allergy 2001; 56: 21–7.
5. Zuberbier T, Asero R, Bindslev-Jensen C. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1418–26.
6. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 2008; 7: 41–53.
7. Das AK, Yoshimura S, Mishima R et al. Stimulation of histamine H1 receptor up-regulates histamine H1-receptor itself through activation of receptor gene transcription. J Pharmacol Sci 2007; 103: 374–82.
8. Simons FER. Advances in H1-antihistamines. N Engl J Med 2004; 351: 2203–17.
9. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133–42.
10. Canonica GW, Blaiss M. Antihistaminic, anti-Inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. WAO Journal 2011; 4: 47–53.
11. Greasley PJ, Clapham JC. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 2006; 553: 1–9.
12. Scadding G. Predicting and establishing the clinical efficacy of a histamine H1- receptor antagonist: desloratadine, the model paradigm. Clin Drug Invest 2005; 25: 153–64.
13. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 2002; 32: 489–98.
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Авторы
Н.И.Ильина, К.С.Павлова*
ФГБУ Государственный научный центр Институт иммунологии ФМБА России. 115478, Россия, Москва, Каширское ш., д. 24, корп. 2
*ksenimedical@gmail.com
Institute of Immunology. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 24, korp. 2
*ksenimedical@gmail.com
ФГБУ Государственный научный центр Институт иммунологии ФМБА России. 115478, Россия, Москва, Каширское ш., д. 24, корп. 2
*ksenimedical@gmail.com
________________________________________________
Institute of Immunology. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 24, korp. 2
*ksenimedical@gmail.com
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