Advertisement

Journal of Clinical Immunology

, Volume 27, Issue 6, pp 605–612 | Cite as

Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis

  • Ali Emad
  • Yasaman Emad
Article

Abstract

Objective

Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF).

Patients

Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group.

Intervention

Pulmonary function tests, tests for DLCO, computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases.

Results

Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too.

Conclusion

A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C–C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

Keywords

Rantes IL-5 eotaxin pulmonary fibrosis mustard 

References

  1. 1.
    Aasted A, Darre E, Wulf HC. Mustard gas: clinical, toxicological and mutagenic aspects based on modern experience. Ann Plast Surg 1987;19:330–33.PubMedCrossRefGoogle Scholar
  2. 2.
    Calvet JH, Jarreau HP, Levame M, Lorino H, d’Ortho MP, Harf A, et al. Acute and chronic effects of sulfur mustard intoxication in the guinea pig. J Appl Physiol 1994;76:681–8.PubMedGoogle Scholar
  3. 3.
    Papirmeister B, Gross CL, Meier HL, Petrali JP, Johnson JB. Molecular basis for mustard-induced vesication. Fundam Appl Toxicol 1985;5:S134–49.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson DR, Byers SL, Vesely KR. Treatment of sulfur mustard (HD)-induced lung injuries. J Appl Toxicol 2000;20:S129.PubMedCrossRefGoogle Scholar
  5. 5.
    Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest 1997;112:734–8.PubMedGoogle Scholar
  6. 6.
    Emad A, Rezaian GR. Characteristics of bronchoalveolar lavage fluid in patients with sulfur mustard gas-induced asthma or chronic bronchitis. Am J Med 1999;106:689–90.CrossRefGoogle Scholar
  7. 7.
    Emad A, Rezaian GR. Immunoglobulins and cellular constituents of the BAL fluid of patients with sulfur mustard gas-Induced pulmonary fibrosis. Chest 1999;115:1346–51.PubMedCrossRefGoogle Scholar
  8. 8.
    Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest 1997;112:734–8.PubMedGoogle Scholar
  9. 9.
    Czarnobilska E, Obtulowicz K. Eosinophil in allergic and non-allergic inflammation. Przegl Lek 2005;62(12):1484–7.PubMedGoogle Scholar
  10. 10.
    Worthylake RA, Burridge K. Leukocyte transendothelial migration: orchestrating the underlying molecular machinery. Curr Opin Cell Biol 2001;31:569–77.CrossRefGoogle Scholar
  11. 11.
    American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000;161:646–64.Google Scholar
  12. 12.
    Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. General considerations for lung function testing. Eur Respir J 2005;26:153–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Cotes JE, Chinn DJ, Quanjer PhH, Roca J, Yernault J-C. Standardization of the measurement of transfer factor (diffusing capacity). Report working party, Standardization of lung function tests, European Community for steel and coal. Official Statement of the European Respiratory Society. Eur Respir J 1993:41–52.Google Scholar
  14. 14.
    Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J 2005;26:948–68.PubMedCrossRefGoogle Scholar
  15. 15.
    Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med 2002;8:435–40 (Sep, review).PubMedCrossRefGoogle Scholar
  16. 16.
    Emad A, Emad Y. Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis. Res Med 2007;101:786–92.CrossRefGoogle Scholar
  17. 17.
    Emad A, Emad Y. Levels of cytokines in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J Interferon Cytokine Res 2007;27:38–43.PubMedCrossRefGoogle Scholar
  18. 18.
    Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001;345:517.PubMedCrossRefGoogle Scholar
  19. 19.
    Moser B, Willimann K. Chemokines: role in inflammation and immune surveillance. Ann Rheum Dis 2004;63:84–9.CrossRefGoogle Scholar
  20. 20.
    Anonymous. Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. The BAL Cooperative Group Steering Committee. Am Rev Respir Dis 1990;141:S169–S202.Google Scholar
  21. 21.
    Manzo A, Caporali R, Montecucco C, Pitzalis C. Role of chemokines and chemokine receptors in regulating specific leukocyte trafficking in the immune/inflammatory response. Clin Exp Rheumatol 2003;21:501–8.PubMedGoogle Scholar
  22. 22.
    Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol. 2002;283:R7–28.PubMedGoogle Scholar
  23. 23.
    Ahn YT, Huang B, McPherson L, Clayberger C, Krensky AM. Dynamic interplay of transcriptional machinery and chromatin regulates “late” expression of the chemokine RANTES in T lymphocytes. Mol Cell Biol 2007;27:253–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Chiba T, Kamada Y, Saito N, Oyamada H, Ueki S, Kobayashi Y, et al. RANTES and eotaxin enhance CD11b and CD18 expression on eosinophils from allergic patients with eosinophilia in the application of whole blood flow cytometry analysis. Int Arch Allergy Immunol 2005;137 Suppl 1:12–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Costa GG, Silva RM, Franco-Penteado CF, Antunes E, Ferreira HH. Interactions between eotaxin and interleukin-5 in the chemotaxis of primed and non-primed human eosinophils. Eur J Pharmacol 2007; 566:200–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Itakura A, Kikuchi Y, Kouro T, Ikutani M, Takaki S, Askenase PW, et al. Interleukin 5 plays an essential role in elicitation of contact sensitivity through dual effects on eosinophils and B-1 cells. Int Arch Allergy Immunol 2006;140 Suppl 1:8–16.PubMedCrossRefGoogle Scholar
  27. 27.
    Umetsu DT. Revising the immunological theories of asthma and allergy. Lancet 2005;365(9454):98–100 (Jan 8–14).PubMedCrossRefGoogle Scholar
  28. 28.
    Kaatz M, Berod L, Czech W, Idzko M, Lagadari M, Bauer A, et al. Interleukin-5, interleukin-3 and granulocyte–macrophage colony-stimulating factor prime actin-polymerization in human eosinophils: a study with hypodense and normodense eosinophils from patients with atopic dermatitis. Int J Mol Med 2004;14 (6):1055–60.PubMedGoogle Scholar
  29. 29.
    Fulkerson PC, Fischetti CA, McBride ML, Hassman LM, Hogan SP, Rothenberg ME. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci USA 2006;103(44):16418–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Lampinen M, Rak S, Venge P. The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 1999;29:314–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Ebisawa M, Yamada T, Bickel C, Klunk D, Schleimer RP. Eosinophil transendothelial migration induced by cytokines. III. Effect of the chemokine RANTES. J Immunol 1994;153:2153–60.PubMedGoogle Scholar
  32. 32.
    Alam R, Stafford S, Forsythe P, Grant GA. RANTES is a chemotactic and activating factor for eosinophils. J Immunol 1993;150:3442–7.PubMedGoogle Scholar
  33. 33.
    Moore BB, Coffey MJ, Christensen P, Sitterding S, Ngan R, Wilke CA, et al. GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism. J Immunol 2000;165:4032–9.PubMedGoogle Scholar
  34. 34.
    Hao H, Cohen DA, Jennings CD, Bryson JS, Kaplan AM. Bleomycin-induced pulmonary fibrosis is independent of eosinophils. J Leukoc Biol 2000;68:515–21.PubMedGoogle Scholar
  35. 35.
    Dombrowicz D, Capron M. Eosinophils, allergy and parasites. Curr Opin Immunol 2001;13:716.PubMedCrossRefGoogle Scholar
  36. 36.
    Boomars KA, Wagenaar SS, Mulder PG, van Velzen-Blad H, van den Bosch JM. Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis. Thorax 1995;50:1087–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhang K, Gharaee-Kermani M, Jones ML, Warren JS, Phan SH. Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis. J Immunol 1994;153:4733–41.PubMedGoogle Scholar
  38. 38.
    Zhang K, Flanders KC, Phan SH. Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis. Am J Pathol 1995;147:352–61.PubMedGoogle Scholar
  39. 39.
    Zhang K, Gharaee Kermani M, McGarry B, Remick D, Phan SH. TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis. J Immunol 1997;158:954–9.PubMedGoogle Scholar
  40. 40.
    Coker RK, Laurent GJ, Shahzeidi S, Lympany PA, du Bois RM, Jeffery PK, et al. Transforming growth factors-β[1], -β[2], and -β[3] stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. Am J Pathol 1997;150:981–91.PubMedGoogle Scholar
  41. 41.
    Rochester CL, Ackerman SJ, Zheng T, Elias JA. Eosinophil-fibroblast interactions. Granule major basic protein interacts with IL-1 and transforming growth factor-beta in the stimulation of lung fibroblast IL-6-type cytokine production. J Immunol 1996;156:4449–56.PubMedGoogle Scholar
  42. 42.
    Shlopov BV, Hasty KA. Collagenase expression by normal human eosinophils. J Leukoc Biol 1998;63:451–5.PubMedGoogle Scholar
  43. 43.
    Cantin A, Fells G, Given JT, Nichols WK, Crystal RG. Sensitivity of the lung to oxidants: cells of the lower respiratory tract are relatively deficient in scavengers of H202. Am Rev Respir Dis 1993;127:163.Google Scholar
  44. 44.
    Kodama N, Yamaguchi E, Hizawa N, Furuya K, Kojima J, Oguri M, et al. Expression of RANTES by bronchoalveolar lavage cells in nonsmoking patients with interstitial lung diseases. Am J Respir Cell Mol Biol 1998;18:526–31.PubMedGoogle Scholar
  45. 45.
    Walker C, Bauer W, Braun RK, Menz G, Braun P, Schwarz F, et al. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 1994;150:1038–48.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Internal Medicine, Section of Pulmonary DiseasesShiraz University of Medical SciencesShirazIran
  2. 2.Shiraz UniversityShirazIran

Personalised recommendations