title: Immunology of fibrotic lung disease: managing infections whilst preventing autoimmunity?
abstract: Interstitial lung disease (ILD) and lung fibrosis are characterized by different grades of fibrosis and inflammation. Persistent low-grade inflammation is believed to play a major pathogenic role, leading to an imbalance of cytokines, growth factors, and tissue proteinases. Recruited monocytes and macrophages play a pivotal role through their cytokine expression and possibly differentiation into fibrocytes, pericytes, or myofibroblasts. Atypical bacterial infections can cause ILD, although not usually in the form of usual interstitial pneumonia. On the other hand, bacterial colonization is frequently encountered in patients with chronic fibrotic lung disorders, and patients regularly undergo antibacterial treatment. As demonstrated in patients with diffuse panbronchiolitis and other chronic respiratory disorders, treatment with macrolides can be beneficial. This is partly explained by their antimicrobial effects but, for macrolides, immunomodulatory properties have been identified which might also be beneficial in patients with ILD or lung fibrosis. This article reviews the immunology of lung fibrogenesis and putative implications of macrolides for reinstallation of tolerance.
authors.affiliation: Department of Rheumatology, Felix-Platter-Spital, University of Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hügle
references.citation: J Clin Invest. 2004 Aug;114(3):438-46
references.pmid: 15286810
references.citation: N Engl J Med. 1986 May 22;314(21):1343-7
references.pmid: 3702942
references.citation: J Pathol. 2005 Jul;206(3):279-90
references.pmid: 15887294
references.citation: Arthritis Rheum. 2010 Jul;62(7):2109-16
references.pmid: 20506251
references.citation: Hum Pathol. 2007 Jan;38(1):147-53
references.pmid: 16996565
references.citation: Semin Liver Dis. 2010 Aug;30(3):245-57
references.pmid: 20665377
references.citation: Curr Opin Rheumatol. 2001 Nov;13(6):505-11
references.pmid: 11698729
references.citation: N Engl J Med. 2001 Aug 16;345(7):517-25
references.pmid: 11519507
references.citation: Curr Opin Infect Dis. 2005 Apr;18(2):125-31
references.pmid: 15735416
references.citation: Mucosal Immunol. 2010 May;3(3):239-46
references.pmid: 20200511
references.citation: Chest. 2009 Nov;136(5):1397-1405
references.pmid: 19892679
references.citation: Am J Respir Cell Mol Biol. 2007 Jan;36(1):43-52
references.pmid: 16902192
references.citation: Curr Pharm Des. 2004;10(25):3045-53
references.pmid: 15544496
references.citation: Chest. 2004 Feb;125(2 Suppl):62S-69S; quiz 69S
references.pmid: 14872002
references.citation: Expert Rev Mol Diagn. 2010 Mar;10(2):187-96
references.pmid: 20214537
references.citation: Am J Respir Crit Care Med. 1997 May;155(5):1763-9
references.pmid: 9154889
references.citation: Curr Pharm Des. 2004;10(25):3067-80
references.pmid: 15544498
references.citation: Am Rev Respir Dis. 1990 Jan;141(1):129-33
references.pmid: 2153352
references.citation: J Clin Invest. 1977 Jan;59(1):165-75
references.pmid: 830661
references.citation: Free Radic Biol Med. 1997;22(1-2):287-305
references.pmid: 8958154
references.citation: JAMA. 2003 Oct 1;290(13):1749-56
references.pmid: 14519709
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Suppl):S93-7
references.pmid: 14503564
references.citation: J Immunol. 1992 Mar 15;148(6):1792-6
references.pmid: 1541819
references.citation: Curr Opin Immunol. 2010 Dec;22(6):761-7
references.pmid: 21087847
references.citation: Ann Rheum Dis. 1995 Jun;54(6):505-10
references.pmid: 7632097
references.citation: Lab Invest. 2007 Sep;87(9):858-70
references.pmid: 17607298
references.citation: Arthritis Rheum. 2011 Mar;63(3):795-9
references.pmid: 21360509
references.citation: Lab Invest. 1992 Feb;66(2):231-42
references.pmid: 1370968
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2426-31
references.pmid: 12606720
references.citation: Chest. 1986 Mar;89(3 Suppl):115S-121S
references.pmid: 3948572
references.citation: Am J Respir Crit Care Med. 2002 Jan 15;165(2):277-304
references.pmid: 11790668
references.citation: Chest. 2010 Sep;138(3):730-3
references.pmid: 20822996
references.citation: Lab Invest. 2010 Jun;90(6):812-23
references.pmid: 20404807
references.citation: J Antimicrob Chemother. 2002 May;49(5):745-55
references.pmid: 12003967
references.citation: J Immunol. 2009 Jan 1;182(1):657-65
references.pmid: 19109199
references.citation: Am J Pathol. 2005 May;166(5):1321-32
references.pmid: 15855634
references.citation: J Immunol. 2001 Jun 15;166(12):7556-62
references.pmid: 11390511
references.citation: Curr Opin Immunol. 2010 Feb;22(1):73-7
references.pmid: 20144855
references.citation: Am J Pathol. 1996 Apr;148(4):1275-82
references.pmid: 8644868
references.citation: Am J Physiol. 1997 Sep;273(3 Pt 1):L676-83
references.pmid: 9316504
references.citation: FEBS Lett. 1997 Jun 30;410(2-3):160-4
references.pmid: 9237621
references.citation: Am J Pathol. 1995 Oct;147(4):1001-15
references.pmid: 7573346
references.citation: Gen Pharmacol. 1997 Oct;29(4):605-9
references.pmid: 9352310
references.citation: Am J Respir Crit Care Med. 2009 Jul 15;180(2):167-75
references.pmid: 19363140
references.citation: Am J Respir Cell Mol Biol. 2006 Aug;35(2):175-81
references.pmid: 16543609
references.citation: Am J Med. 2004 Nov 8;117 Suppl 9A:5S-11S
references.pmid: 15586558
references.citation: J Immunol. 2010 Aug 15;185(4):2502-15
references.pmid: 20624949
references.citation: Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii40-4
references.pmid: 19487223
references.citation: J Antimicrob Chemother. 2004 Jul;54(1):21-8
references.pmid: 15190022
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13180-5
references.pmid: 16924102
references.citation: Eur Respir J. 1997 Apr;10(4):787-94
references.pmid: 9150314
references.citation: Science. 2007 Aug 3;317(5838):666-70
references.pmid: 17673663
references.citation: Pathol Res Pract. 2006;202(5):373-8
references.pmid: 16488088
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2000 Oct;17(3):229-38
references.pmid: 11033838
references.citation: Autoimmun Rev. 2011 Mar;10(5):248-55
references.pmid: 20863911
references.citation: Cell. 2010 Mar 19;140(6):771-6
references.pmid: 20303867