Effect of N-acetylcysteine on mucosal immunity of respiratory tract


Cite item

Full Text

Abstract

The outcome of diseases accompanied or caused by mucostasis depends both on the restoration of drainage function of the airways and on the effectiveness of immune mechanisms against pathogens. N-acetylcysteine (NAC) is widely used as mucolytic and antioxidant remedy in clinical practice. In this regard, the data of the scientific literature on the direct and indirect effects of NAC on the mucosal immunity of the respiratory tract have been reviewed. NAC possesses pleiotropic immunomodulating properties, most of which contribute to the regression of clinical manifestations of acute and chronic inflammatory diseases of the respiratory tract. Biological and pharmacological effects of NAC include improvement in rheological properties of mucus, reduction of excess mucin production, restoration of mucociliary clearance and production of sIgA, suppression of excess production of IgE and IgG4, destruction of biofilms and inhibition of their formation, suppression of adhesion of pathogenic bacteria to epithelial cells, antioxidant activity, regulation of the production of pro-inflammatory and profibrotic cytokines. There was no convincing evidence that NAC is able to suppress any component of mucosal immunity. For final conclusions on this subject, further research are required.

About the authors

O V Kalyuzhin

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: kalyuzhin@list.ru
д.м.н., проф., проф. каф. клинической иммунологии и аллергологии; ORCID ID: https://orcid.org/0000-0003-3628-2436 Moscow, Russia

References

  1. Анаев Э.Х. Муколитическая терапия: рациональный выбор. Эффективная фармакотерапия. 2010; (27): 25-28.
  2. Геппе Н.А., Снегоцкая М.Н., Никитенко А.А. Ацетилцистеин для лечения кашля у детей // Педиатрия. Прил. к журналу Consilium Medicum. 2007;(2):43-47.
  3. Зайцева О.В. Муколитические препараты в терапии болезней органов дыхания у детей: современный взгляд на проблему. Русский медицинский журнал. 2003; 11 (1): 49-54.
  4. Коровина Н.А., Захарова И.Н., Заплатников А.Л., Овсянникова Е.М. Противокашлевые и отхаркивающие лекарственные средства в практике врача - педиатра: рациональный выбор и тактика применения. Пособие для врачей. - Москва: РМАПО, 2002.
  5. Knowles M.R, Boucher R.C. Mucus clearance as a primary innate defense mechanism for mammalian airways. The Journal of Clinical Investigation. 2002; 109 (5): 571-577. https://doi.org/10.1172/jci15217
  6. Dreisin R.B, Mostow S.R. Sulfhydryl - mediated depression of ciliary activity: an adverse effect of acetylcysteine. J Lab Clin Med. 1979; 93 (4): 674-678.
  7. Roomans G.M, Tegner H, Toremalm N.G. Acetylcysteine and its derivatives: functional and morphological effects on tracheal mucosa in vitro. Eur J Respir Dis. 1983; 64 (6): 416-425.
  8. Olivieri D, Marsico S.A, Del Donno M. Improvement of mucociliary transport in smokers by mucolytics. Eur J Respir Dis Suppl. 1985; 139: 142-145.
  9. Stafanger G, Garne S, Howitz P, Morkassel E, Koch C. В The clinical effect and the effect on the ciliary motility of oral N-acetylcysteine in patients with cystic fibrosis and primary ciliary dyskinesia. Eur Respir J.1988; 1 (2): 161-167.
  10. Mata M, Sarrion I, Armengot M, Carda C, Martinez I, Melero J.A, Cortijo J. Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells: Effectiveness of N-Acetylcysteine. Chu HW, ed. PLoS ONE. 2012; 7 (10): e48037. https://doi.org/10.1371/journal.pone.0048037
  11. Corthesy B. Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces. Future Microbiol. 2010; 5: 817-29. https://doi.org/10.2217/fmb.10.39
  12. Mathias A, Pais B, Favre L, Benyacoub J, Corthésy B. Role of secretory IgA in the mucosal sensing of commensal bacteria. Gut Microbes. 2014; 5 (6): 688-695. https://doi.org/10.4161/19490976.2014.983763
  13. Stone K.D, Prussin C, Metcalfe D.D. IgE, Mast Cells, Basophils, and Eosinophils. The Journal of allergy and clinical immunology. 2010; 125 (2 Suppl 2): S73-S80. https://doi.org/10.1016/j.jaci.2009.11.017
  14. Della-Torre E, Lanzillotta M, Doglioni C. Immunology of IgG4-related disease. Clinical and Experimental Immunology. 2015; 181 (2):191-206. https://doi.org/10.1111/cei.12641
  15. Perugino C.A, Mattoo H, Mahajan V.S, Maehara T, Wallace Z.S, Pillai S, Stone J.H. Emerging Treatment Models in Rheumatology: IgG4-Related Disease: Insights into human immunology and targeted therapies. Arthritis Rheumatol. 2017; 69(9): 1722-1732. https://doi.org/10.1002/ art. 40365
  16. Kato A, Hulse K.E, Tan B.K, Schleimer R.P. B lymphocyte lineage cells and the respiratory system. The Journal of allergy and clinical immunology. 2013; 131 (4): 933-957. https://doi.org/10.1016/j.jaci. 2013.02.023
  17. Jeannin P, Delneste Y, Lecoanet-Henchoz S, Gauchat J.F, Life P, Holmes D, Bonnefoy J.Y. Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis. The Journal of Experimental Medicine. 1995; 182 (6): 1785-1792. https://doi.org/ 10.1084/jem.182.6.1785
  18. Yanagihara Y, Basaki Y, Kajiwara K, Ikizawa K. A thiol antioxidant regulates IgE isotype switching by inhibiting activation of nuclear factor - κB. J Allergy Clin Immunol. 1997; 100: 33-38. https://doi.org/ 10.1016/s0091-6749(97)70002-2
  19. Giordani L, Quaranta M.G, Malorni W, Boccanera M, Giacomini E, Viora M. N-acetylcysteine inhibits the induction of an antigen - specific antibody response down - regulating CD40 and CD27 co - stimulatory molecules. Clin Exp Immunol. 2002; 129 (2): 254-264. https://doi.org/ 10.1046/j.1365-2249.2002.01897.x
  20. Ercal N, Neal R, Treeratphan P, Lutz P.M, Hammond T.C, Dennery P.A, Spitz D.R. A role for oxidative stress in suppressing serum immunoglobulin levels in lead - exposed Fisher 344 rats. Arch Environ Contam Toxicol. 2000; 39 (2): 251-256. https://doi.org/10.1007/ s002440010102
  21. Wang J, Li Q, Xie J, Xu Y. Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses in the lung during influenza virus infection. Respiratory Research. 2015; 16 (1): 37. https://doi.org/ 10.1186/s12931-015-0201-y
  22. Ragland S.A, Criss A.K. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. Bliska J.B, ed. PLoS Pathogens. 2017; 13 (9): e1006512. https://doi.org/10.1371/journal. ppat.1006512
  23. Tse H.N, Tseng C.Z.S. Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease. 2014; 9: 825-836. https://doi.org/10.2147/copd. s51057
  24. Eklund A, Eriksson O, Hakansson L et al. Oral N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: correlation to effects on cellular variables. Eur Respir J. 1988; 1 (9): 832-838.
  25. Walters M.T, Rubin C.E, Keightley S.J. A double - blind, cross - over, study of oral N-acetylcysteine in Sjögren’s syndrome. Scand J Rheumatol Suppl. 1986 61: 253-258.
  26. An J-Y, Lee H-N, Park K-I, Kim J-Y, Lee J-Y, Park K-H. Effects of N-acetylcysteine (NAC) on non - specific immune parameters, respiratory burst and lysozyme activities, in different fishes. Journal of fish pathology. 2012; 25: 1-10. http://dx.doi.org/10.7847/jfp.2012.25.1.001
  27. Monick M.M, Samavati L, Butler N.S, Mohning M, Powers L.S, Yarovinsky T, Spitz D.R, Hunninghake G.W. Intracellular thiols contribute to Th2 function via a positive role in IL-4 production. J Immunol. 2003; 171 (10): 5107-5115. https://doi.org/10.4049/jimmunol. 171.10.5107
  28. Elferink J.G, de Koster B.M. N-acetylcysteine causes a transient stimulation of neutrophil migration. Immunopharmacology. 1998; 38 (3): 229-236. https://doi.org/10.1016/s0162-3109(97)00056-8
  29. Hasan M.A, Ahn W-G, Song D-K. N-acetyl-L-cysteine and cysteine increase intracellular calcium concentration in human neutrophils. Korean J Physiol Pharmacol. 2016; 20 (5): 449-457. https://doi.org/ 10.4196/kjpp.2016.20.5.449
  30. Heller A.R, Groth G, Heller S.C, Breitkreutz R, Nebe T, Quintel M, Koch T. N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients. Crit Care Med. 2001; 29 (2): 272-276. https://doi.org/10.1097/00003246-200102000-00009
  31. Paulsen O, Forsgren A. Effects of N-acetylcysteine on human polymorphonuclear leukocytes. APMIS. 1989; 97 (2): 115-119. https://doi. org/10.1111/j.1699-0463.1989.tb00764.x
  32. Linden M, Wieslander E, Eklund A, Larsson K, Brattsand R. Effects of oral N-acetylcysteine on cell content and macrophage function in bronchoalveolar lavage from healthy smokers. Eur Respir J. 1988; 1 (7): 645-650.
  33. Pinar Karapinar S, Ulum Y.Z, Ozcelik B, Dogan Buzoglu H, Ceyhan D, Balci Peynircioglu B, Aksoy Y. The effect of N-acetylcysteine and calcium hydroxide on TNF-α and TGF-β1 in lipopolysaccharide - activated macrophages. Arch Oral Biol. 2016; 68: 48-54. https://doi.org/ 10.1016/j.archoralbio.2016.03.017
  34. Gosset P, Wallaert B, Tonnel A.B, Fourneau C. Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages. Eur Respir J. 1999; 14 (1): 98-105. https://doi.org/ 10.1034/j.1399-3003.1999.14a17.x
  35. Cu A, Ye Q, Sarria R, Nakamura S, Guzman J, Costabel U. N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. Sarcoidosis Vasc Diffuse Lung Dis. 2009; 26 (2): 147-154.
  36. Riise G.C, Qvarfordt I, Larsson S, Eliasson V, Andersson B.A. Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration. 2000; 67 (5): 552-558. https://doi.org/ 10.1159/000067473
  37. Zheng C.H, Ahmed K, Rikitomi N, Martinez G, Nagatake T. The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells. Microbiol Immunol. 1999; 43 (2): 107-13. https://doi.org/10.1111/j.1348-0421.1999.tb02381.x
  38. Olofsson A.C, Hermansson M, Elwing H. N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces. Appl Environ Microbiol. 2003; 69: 4814-4822. https://doi.org/10.1128/aem.69.8.4814-4822.2003
  39. Marchese A, Bozzolasco M, Gualco L, Debbia E.A, Schito G.C, Schito A.M. Effect of fosfomycin alone and in combination with N-acetylcysteine on E. coli biofilms. Int J Antimicrob Agents. 2003; 22 (Suppl 2): 95-100. https://doi.org/10.1016/s0924-8579(03)00232-2
  40. Perez-Giraldo C, Rodríguez-Benito A, Morán F.J, Hurtado C, Blanco M.T, Gómez-García A.C. Influence of N-acetylcysteine on the formation of biofilm by Staphylococcus epidermidis. J Antimicrob Chemother. 1997; 39: 643-646. https://doi.org/10.1093/jac/39.5.643
  41. del Prado G, Ruiz V, Naves P, Rodríguez-Cerrato V, Soriano F, del Carmen Ponte M. Biofilm formation by Streptococcus pneumoniae strains and effects of human serum albumin, ibuprofen, N-acetyl - l - cysteine, amoxicillin, erythromycin, and levofloxacin. Diagn Microbiol Infect Dis. 2010; 67: 311-318. https://doi.org/10.1016/j.diagmicrobio.2010.03.016
  42. Zhao T, Liu Y. N-acetylcysteine inhibit biofilms produced by Pseudomonas aeruginosa. BMC Microbiol. 2010; 10: 140. https://doi. org/10.1186/1471-2180-10-140
  43. Blasi F, Page C, Rossolini G.M, Pallecchi L, Matera M.G, Rogliani P, Cazzola M. The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 2016; 117: 190-197. https://doi.org/10.1016/j.rmed.2016.06.015
  44. Dinicola S, De Grazia S, Carlomagno G, Pintucci J.P. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. Asystematicreview. Eur Rev Med Pharmacol Sci. 2014; 18 (19): 2942-2948.
  45. Domenech M, García E. N-Acetyl - l - Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae. Antimicrobial Agents and Chemotherapy. 2017; 61 (2): e01992-16. https://doi.org/ 10.1128/aac.01992-16
  46. Valle J, Latasa C, Gil C, Toledo-Arana A, Solano C, Penadés J.R, Lasa I. Bap, a Biofilm Matrix Protein of Staphylococcus aureus Prevents Cellular Internalization through Bindingto GP96 HostReceptor. PLoS Pathogens. 2012; 8 (8): e1002843. https://doi.org/10.1371/journal. ppat.1002843

Copyright (c) 2018 Consilium Medicum

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


This website uses cookies

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

About Cookies