Regarding to the issue of the role of cytokines in the pathogenesis of asthma and the possibilities of anticytokine therapy

Abstract


The study involved 210 people, of which 32 had mild bronchial asthma, 39 had moderate bronchial asthma, 39 had moderate bronchial asthma combined with chronic obstructive pulmonary disease, 38 had chronic obstructive pulmonary disease, 17 patients suffered from community-acquired pneumonia, 25 patients with essential hypertension and ischemic heart disease (comparison group) and 20 healthy patients. We assessed sIgE to mite allergens, dust allergens, and the mixed grass, trees, weeds and flower pollen allergens , Str. pneumon., Haemofil. influenzae, Neisseria perflava. The levels of interleukin-4, interleukin6, interleukinlO, interleukin-7, gamma-interferon, tumor necrosis factor were investigated. All patients were studied in the acute condition of the disease. We assessed the infectious potential and atopic potential in every patient. Results of the study allow to resume that cytokines levels, their combinations (cytokine profile) testing has not to be advisable for clinical diagnostics, assessement of the severity of the disease and treatment strategy including anti-cytokine therapy.

Становится все более очевидной чрезвычайная гетерогенность бронхиальной астмы (БА). Более 30 лет назад, в 1977 г., мы указывали на наличие у больных БА семи клинико-патогенетических вариантов течения БА, названных в последующем фенотипами: инфекционнозависимого, атопического, гормонального, нервно-психического, аутоиммунного, выраженного адренергического дисбаланса и первично измененной реактивности бронхов [1]. Для каждого из этих вариантов были разработаны методы индивидуальной диагностики и терапии, результаты их апробации неоднократно публиковались. В последующем формулировка «первично измененная реактивность бронхов» была заменена на представления о БА физического усилия, дизовари-альном и аспириновом клинико-патогенетических вариантах (фенотипах) БА, совершенствовались методы индивидуальной диагностики и терапии, и повышалась их эффективность.

G B Fedoseev

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: fedoseevsp@mail.ru
Russia

V I Trofimov

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

K V Negrutsa

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

V G Timchik

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

V I Golubeva

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

V A Aleksandrin

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

T S Razumovskaya

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

K N Kryakunov

Academician I.P. Pavlov First St. Petersburg State Medical University

Russia

  1. Федосеев Г.Б., Коровина О.В., Тенигина Н.Г. Комплексная диагностика различных клинико-патогенетических вариантов бронхиальной астмы. Терапевтический архив. 1977, № 6, с. 51-55.
  2. Adcock I.M., Lane S.J. Corticosteroid-insensitive asthma: molecular mechanisms. J. Endocrinol. 2003, v. 178, p. 347-355.
  3. Icuhara K., Matsumoto H., Ohta S. et al. Recent developments regarding periostin in bronchial asthma. Allergol. Int. 2015, v. 64, p. 3-10.
  4. Desai M., Oppenheimer J. Elucidating asthma phenotypes and endotypes: progress towards personalized medicine. Annals Allergy Asthma Immunol. 2016, v. 116, p. 394-401.
  5. Wenzel S.E. Asthma phenotypes: evolution from clinical to molecular approaches. Nat. Med. 2012, v. 18, p. 716-725.
  6. Muraro A., Lemanske R.F., Hellings P.W. et al. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis - PRACTALL documents of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. J. Allergy Clin. Immumology. 2016, v. 137, p. 1347-1358.
  7. Simpson J.L., Scott R., Boyle M.J., Gibson P.G. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006, v. 11, p. 54-61.
  8. Федосеев Г.Б., Трофимов В.И., Негруца К.В. и соавт. Характеристика мокроты для оценки наличия и характера воспаления бронхолегочного аппарата у больных бронхиальной астмой и хронической обструктивной болезнью легких. Рос. Аллергол. Журн. 2015, № 1, с. 15-27.
  9. Zissler U.M., Essenvon Bieren J., Jakwerth C.A., Chaker A.M. Current and future biomarkers in allergic asthma. J. Allergy. 2016, v. 71, p. 475-494.
  10. Hamid Q.A., Minshall E.M. Molecular pathology of allergic disease. J. Allergy Clin. Immunol. 2000, v. 105, p. 20-36.
  11. Moldoveanu B., Otmishi P., Jani P. et al. Inflammatory mechanisms in lung. Inflamm. Res. 2009, v. 2, p. 1-11.
  12. Commins S.P., Borish L., Steinke J.W. Immunologic messenger molecules: Cytokines, interferons and chemokines. J. Allergy Clin. Immunol. 2010, v. 125, p. 53-72.
  13. Rosenwasser L.J., Zimmermann N., Hershey D.K. et al. Chemokines in asthma: Cooperative interaction between chemokines and IL-13. J. Allergy Clin. Immunol. 2003, v. 111, p. 227-242.
  14. Barnes P.J. The cytokine network in asthma and chronic obstructive pulmonary disease. J. Clin. Invest. 2008, v. 118,p. 3546-3556.
  15. Uhm T.G., Kim B.S., Chung I.Y Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in pathogenesis of asthma. Allergy Asthma Immunol. Res. 2012, v. 4, p. 68-79.
  16. Stone K.D., Prussin C., Metcalfe D.D. IgE, mast cells, basophils and eosinophils. J. Allergy Clin. Immunol. 2010, v. 125, p. 73-80.
  17. Varricchi D., Bagnasco D., Borriello F. et al. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr. Opin. Allergy Clin. Immunol. 2016, v. 16, p. 186-200.
  18. Gao P., Simpson J.L., Zhang J., Gibson P.G. Galection-3: its role in asthma and potential as an anti-inflammatory target. Respir. Res. 2013, v. 14, p. 136-145.
  19. Bradding P., Feather I.H., Howarth P.H. et al. Interleukin 4 is localized to and released by human mast cells. J. Exp. Med. 1992, v. 176, p. 1381-1386.
  20. Trevor J., Deshane J.S. Refractory asthma: mechanisms, targets, and therapy. J. Allergy. 2014, v. 69, p. 817-827.
  21. Pelletier M., Maggi L., Micheletti A. et al. Evidence for a crosstalk between human neutrophils and Th17-cells. Blood. 2010, v. 115, p. 335-343.
  22. Cua D.J., Tato C.M. Innate IL-17-producing cells: the sentinels of the immune system. Nat. Rev. Immunol. 2010, v. 10, p. 476-489.
  23. Spits S., Artis D., Colonna M. et al. Innate lymphoid cells a proposal for uniform nomenclature. Nat. Rev. Immunol. 2013, v. 13, p. 145-149.
  24. Roussel L., Houle F., Chan C. et al. IL-17 promotes p38 MARK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J. Immunol. 2010, v. 184, p. 4531-4537.
  25. Takeshita S., Kikuno R., Tezuka K., Amann E. Osteoblast-specific factor 2: doning of a putative bone adhesion protein with homology with the insect protein fasciclin1. Biochem. J. 1993, v. 294, p. 271-178.
  26. Li W., Dao P, Zhi I. et al. Periostin: its role in asthma and its potential as a diagnostic or therapeutic target. Respir. Res. 2015, v. 16, p. 57-68.
  27. Maselli D., Keyt H., Rogers L. Profile of lebrikizimab and its potential in the treatment of asthma. J. Asthma Allergy. 2015, v. 8, p. 87-92.
  28. Nuzzo P.V., Buzzatti G., Ricci V. et al. Periostin: a novel prognostic and therapeutic target for genitourinary cancer? Clin. Genitourin Cancer. 2014, v. 12, p. 301-311.
  29. Tartibi H.M., Bahna S.L. Clinical and biological markers of asthma control. Expert Rev. Clin. Immunol. 2014, v. 10, p. 1453-1461.
  30. Takayama G., Arima K., Kanaji T et al. Periostin: a novel component of subepitelial fibrosis of bronchial asthma donstream of IL-4 and IL-13 signals. J. Allergy Clin. Immunol. 2006, v. 118, p. 98-104.
  31. Uchida M., Shiraishi H., Ohta S. et al. Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis. Am. J. Respir. Cell. Mol. Biol. 2012, v. 46, p. 677-687.
  32. Sakellarion G., Anastasilaks A.D., Bisbinas I. at al. Circulating periostin levels with AS: association with clinical and radiographic variables, markers and molecules involved in bone formation. Rheumatology (Oxford). 2015, v. 54, p. 908-914.
  33. Okamoto M., Hoshino T., Kitasato Y. et al. Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur. Respir. J. 2011, v. 37, p. 1119-1127.
  34. Maer-Ainin M., Abed A., Conway S.J. et al. Inhibition of periostin expression protects against the development of renal inflammation and fibrosis. J. Am. Soc. Nephrol. 2014, v. 25, p. 1714-1736.
  35. Hong L.Z., Wei X.W, Chen J.F., Shi Y. Overexpressen of periostin predicts poor prognosis in non-smoll cell lung cancer. Oncol. Lett. 2013, v. 6, p. 1595-1603.
  36. Blanchard C., Mingler M.K., McBride M. et al. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal. Immunol. 2008, v. 1, p. 289-296.
  37. Masuoka M., Shiraishi H., Ohta S. et al. Periostin promotes chronic allergic inflammation in response to Th2 cytokines. J. Clin. Invest. 2012, v. 122, p. 2590-2600.
  38. Bentley J., Chen Q., Hong J.Y et al. Periostin is required for maximal airways inflammation and hyperresponsiveness in mice. J. Allergy Clin. Immunol. 2014, v. 134, p. 1433-1442.
  39. Choi J.H., Kim M.A., Park H.S. An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease. Curr. Open Allergy Clin. Immunol. 2014, v. 14, p. 1-6.
  40. Johansson M.N., Annis D.S., Mosher D.F. Alpha(M)beta(2) integrin-mediated adhesion and motility of IL-5-stimulated eosinophils on periostin. Am. J. Respir. Cell. Mol. Biol. 2013, v. 48, p. 503-510.
  41. Icuhara K., Matsumoto H., Ohta S. et al. Recent developments regarding periostin in bronchial asthma. Allergol. Int. 2015, v. 64, p. 3-10.
  42. Matsusaka M., Kabata H., Fukunaga K. et al. Phenotype of asthma related with high serum periostin levels. Allergol. Int. 2015, v. 64, p. 175-180.
  43. Kim M., Izuhara K., Ohta J. et al. Association of serum periostin with aspirin-exacerbated reaspiratory disease. Ann. Allergy Asthma Immunol. 2014, v. 113, p. 314-320.
  44. Choi J.H., Kim M.A., Park H.S. An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease. Curr. Opin. Allergy Clin. Immunol. 2014, v. 14, p. 1-6.
  45. Van Zele T., Clayes S., Gevaert P. et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006, v. 61, p. 1280-1289.
  46. Kou K., Okawa T., Yamaguchi Y. et al. Periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis. Br. J. Dermatol. 2014, v. 171, p. 284-291.
  47. Woodruff P.G., Modrek B., Choy D.F. et al. T-helper type 2-drived inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care. Med. 2009, v. 180, p. 388-395.
  48. Corren J., Lemanske R.F., Hanania N.A. et al. Lebrikizumab treatment in adults with asthma. N. Engl. J. Med. 2011, v. 365, p. 1088-1098.
  49. Hanania N., Wenzel S., Rosen K. et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in EXTRA study. Am. J. Respir. Crit. Care. Med. 2013, v. 187, p. 804-811.
  50. Wagener A.H., de Nijs S.B., Lutter R. et al. External validation of blood eosinophils, FE (NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015, v. 70, p. 115-120.
  51. Carr T.F., Kraft M. Update in asthma 2014. Am. J. Respir. Crit. Care Med. 2015, v. 192, p. 157-163.
  52. Manzella F., Lusuardi M., Galeone C., Zucchi L. Tailored therapy for severe asthma. Multidiscip. Respir. Med. 2015, v. 10, p. 1-5.
  53. Castro M., Mathur S., Hargreave F. et al. Reslizumab for poorly controlled eosinophilic asthma: a randomized, placebo-controlled study. Am. J. Respir. Crit. Care. Med. 2011, v. 184, p. 1125-1132.
  54. Walsh G.M. An update on emerging drags for asthma. Expert. Opin. Emerg. Drags. 2012, v. 17, p. 37-42.
  55. Ortega H.G., Liu M.C., Pavord I.D. et al. Mepolizumab treatment in patients with severe eosinophilic asthma. New. Engl. J. Med. 2014, v. 371, p. 1198-1207.
  56. Bel E.H., Wenzel S.E., Thompson P.I. et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. New. Engl. J. Med. 2014, v. 371, p. 1189-1197.
  57. Varricchi G., Begnasco D., Borriello F. et al. Interleucin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr. Opin. Allergy Clin. Immunol. 2016, v. 16, p. 186-200.
  58. Сastro M., Wenzel S.E., Bleecker E.R. et al. Benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomized dose-ranging study. Lancet Respir. Med. 2014, v. 2, p. 879-890.
  59. Sidhu S.S., Yuan S., Innes A.L. et al. Roles of epithelial cell-deriostin periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma. Proc. Natl. Acad. Sci. USA. 2010, v. 107, p. 14170-14175.
  60. Humbert M., Durham S.R., Kimmitt P. et al. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J. Allergy. Clin. Immunol. 1997, v. 99, p. 657-665.
  61. Noonan M., Korenblat P., Mosesona S. et al. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J. Allergy Clin. Immunol. 2013, v. 132, p. 567-574.
  62. Corren J., Busse W., Meltzer E.O. et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am. J. Respir. Crit. Care Med. 2010, v. 181, p. 788-796.
  63. Wenzel S., Ford L., Pearlman D. et al. Dupilumab in persistent asthma with elevated eosinophil levels. New. Engl. J. Med. 2013, v. 368, p. 2455-2466.
  64. Busse W.W., Israel E., Nelson H.S. et al. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am. J. Respir. Crit. Care Med. 2008, v. 178, p. 1002-1008.
  65. De Boever E.H., Ashman C., Cahn A.P. et al. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J. Allergy Clin. Immunol. 2014, v. 133, p. 989-996.
  66. May R.D., Monk P.D., Cohen E.S. et al. Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma. Br. J. Pharmacol. 2012, v. 166, p. 177-193.
  67. Федосеев Г.Б., Трофимов В.И., Тимчик В.Г. и соавт. Инфекционная и неинфекционная сенсибилизация больных бронхиальной астмой и хронической обструктивной болезнью легких. Рос. Аллергол. Журн. 2015, № 6, с. 34-53.

Views

Abstract - 14

PDF (Russian) - 26

PlumX

Dimensions

Refbacks

  • There are currently no refbacks.

Copyright (c) 2016 Russian Allergological Journal

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies