Macrolides and cancer, arthritis and IBD

  • Keiichi Mikasa
  • Kei Kasahara
  • Eiji Kita
Part of the Progress in Inflammation Research book series (PIR)


Inflammatory Bowel Disease Human Bronchial Epithelial Cell Natural Killer Activity Ehrlich Ascites Carcinoma Mycobacterium Paratuberculosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Labro MT (1993) Effects of macrolides on host natural defences. In: AJ Bryskier, JP Butzler, HC Neu, PM Tulkens (eds): Macrolides. Arnette Blackwell, Paris, 389–408Google Scholar
  2. 2.
    Desaki M, Takizawa H, Ohtoshi T, Kasama T, Kobayashi K, Sunazuka T, Omura S, Yamamoto K, Ito K (2000) Erythromycin suppresses nuclear factor-ºB and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun 267: 124–8CrossRefPubMedGoogle Scholar
  3. 3.
    Yamanaka A, Saiki S, Tamura S, Saito K (1969) Problems in chronic obstructive bronchial disease, with special reference to diffuse panbronchiolitis. Naika 23: 442–51PubMedGoogle Scholar
  4. 4.
    Kobayashi H (1995) Airway biofilm disease: clinical manifestations and therapeutic possibilities using macrolides. J Infect Chemother 1: 1–15Google Scholar
  5. 5.
    Sawaki M, Mikami R, Mikasa K, Kunimatsu M, Ito S, Narita N (1986) The long-term chemotherapy with erythromycin in chronic lower respiratory tract infection — first report: comparison with amoxicillin. Kansenshogaku Zasshi 60: 37–44PubMedGoogle Scholar
  6. 6.
    Khair OA, Devalia JL, Abdelaziz MM, Sapsford RJ, Davis RJ (1995) Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J 8: 1451–7Google Scholar
  7. 7.
    Ueda K, Mikasa K, Hamada K, Sakamoto M, Konishi M, Maeda K, Majima T, Kita E, Narita N (1999) Effects of clarithromycin on expression of cytokine mRNA in spleen cells of mice bearing Lewis lung carcinoma cells. Haigan 39: 117–24Google Scholar
  8. 8.
    Mikasa K, Sawaki M, Konishi M, Egawa S, Yoneda T, Yagyu Y, Fujimura M, Hamada K, Kunimatsu M, Narita N (1989) The effect of erythromycin treatment of natural killer (NK) cell activity in patients with chronic lower respiratory tract infections. Kansenshogaku Zasshi 63: 811–15PubMedGoogle Scholar
  9. 9.
    Hamada K, Kita E, Sawaki M, Mikasa K, Narita N (1995) Antitumor effect of erythromycin in mice. Chemotherapy 41: 59–69PubMedGoogle Scholar
  10. 10.
    Hamada K, Mikasa K, Yunou Y, Kurioka T, Majima T, Narita E (2000) Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer. Chemotherapy 46:49–61CrossRefPubMedGoogle Scholar
  11. 11.
    Mikasa K, Sawaki M, Kita E, Hamada K, Teramoto S, Sakamoto M, Maeda K, Konishi M, Narita N (1997) Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin. Chemotherapy 43: 288–96PubMedGoogle Scholar
  12. 12.
    Sawaki M, Kita E, Mikasa K, Narita N (1995) Clarithromycin as a potent ant-angiogenesis agent: possible application for the antitumor agent. Can J Infect Dis 6(Suppl C):213Google Scholar
  13. 13.
    Yatsunami J, Tsuruta N, Wakamatsu K. Hara N, Hayashi S (1997) Clarithromycin is a potent inhibitor of tumor-induced angiogenesis. Res Exp Med 197: 189–97CrossRefGoogle Scholar
  14. 14.
    Yatsunami J, Tsuruta N, Fukuno Y, Kawashima M, Taniguchi S, Hayashi S (1999) Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells. Clin Exp Metastasis 17: 119–24CrossRefPubMedGoogle Scholar
  15. 15.
    Parajuli P, Yano S, Hanibuchi M, Nokihara H, Shinohara T, Sone S (1998) Effect of clarithromycin on the distant metastases of human lung cancer cells in SCID mice. J Med Invest 44: 205–10PubMedGoogle Scholar
  16. 16.
    Teramoto S, Kita E, Mikasa K, Hamada K, Konishi M, Maeda K, Sakamoto M, Tsujimoto M, Mori K, Sawaki M et al (1998) Effect of clarithromycin administration on interferon-gamma and interleukin 12 mRNA expression in the tumor tissue of nonsmall-cell lung cancer. Jpn J Antibiot 51(Suppl): 53–5PubMedGoogle Scholar
  17. 17.
    Sakamoto M, Mikasa K, Majima T, Hamada K, Konishi M, Maeda K, Kita E, Narita N (2001) Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. Chemotherapy 47: 444–51CrossRefPubMedGoogle Scholar
  18. 18.
    Sasaki M, Ito T, Fukui S, Izumiyama N, Kashima M, Sano M, Fujiwara Y, Miura H (2001) Effect of 14-membered ring macrolides on heparanase mRNA expression in lung cancer cells. Jpn J Antibiot (Suppl): 54: C97–100Google Scholar
  19. 19.
    Sasaki M, Kashima M, Ito T, Watanabe A, Sano M, Kagaya M, Shioya T, Miura M (2000) Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity. Mediators Inflamm 9: 85–91CrossRefPubMedGoogle Scholar
  20. 20.
    Lapierre F, Holme K, Lam L, Tressler RJ, Storm N, Wee J, Stack RJ, Castellot J, Tyrrell D (1996) Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties. Glycobiol 6: 355–66Google Scholar
  21. 21.
    Nakajima M, Irimura T, Nicolson GL (1988) Heparanases and tumor metastasis. J Biol Chem 36: 157–67Google Scholar
  22. 22.
    Vaday GG, Lider O (2000) Extracellular matrix miotics, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol 67: 149–59PubMedGoogle Scholar
  23. 23.
    Nakajima M, Irimura T, Di Ferrante N, Nicolson GL (1984) Metastatic melanoma cell heparanase. Characterization of heparan sulphate degradation fragments produced by B16 melanoma endoglucuronidase. J Biol Chem 259: 2283–90PubMedGoogle Scholar
  24. 24.
    Vlodavsky I, Friedman Y, Elkin M, Aingorn H, Atzmon R, Ishai-Michaeli R, Bitan M, Pappo O, Peretz T, Michal I et al (1999) Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med 5: 793–802CrossRefPubMedGoogle Scholar
  25. 25.
    Hulett MD, Freeman C, Hamdorf BJ, Baker RT, Harris MJ, Parish CR (1999) Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med 5: 803–9CrossRefPubMedGoogle Scholar
  26. 26.
    Kita E, Mikasa K, Kasahara K (2003) Syndecan shedding from epithelial cells affects host defense against respiratory infection. International Congress Series 1257C:21–5CrossRefGoogle Scholar
  27. 27.
    Joensuu H, Anttonen A, Eriksson M, Mäkitaro R, Alfthan H, Kinnula V, Leppä S (2002) Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer. Cancer Res 62: 5210–17PubMedGoogle Scholar
  28. 28.
    Anttonen A, Leppa S, Ruotsalainen T, Alfthan H, Mattson K, Joensuu H (2003) Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer 41: 171–7CrossRefPubMedGoogle Scholar
  29. 29.
    Tsutsumi M, Kitada H, Shiraiwa K, Takahama M, Tsujiuchi T, Sakitani H, Sasaki Y, Murakawa K, Yoshimoto M, Konishi Y (2000) Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis (2-hydroxypropyl) amine in rats. Carcinogenesis 21: 251–6CrossRefPubMedGoogle Scholar
  30. 30.
    Li Q, Park PW, Wilson CL, Parks WC (2002) Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 111: 635–46CrossRefPubMedGoogle Scholar
  31. 31.
    Tjan-Heijnen VCG, Postmus PE, Ardizzoni A, Manegold CH, Burghouts J, van Meerbeeck J, Gans S, Mollers M, Buchholz E, Biesma B et al (2001) Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study. Ann Oncol 12: 1359–68CrossRefPubMedGoogle Scholar
  32. 32.
    Alder J, Mitten M, Jarvis K, Gupta P, Clement J (1993) Efficacy of clarithromycin for treatment of experimental Lyme disease in vivo. Antimicrob Agents Chemother 37:1329–33PubMedGoogle Scholar
  33. 33.
    Tissi L, von Hunolstein C, Mosci P, Campanelli C, Bistoni F, Orefici G (1995) In vivo efficacy of azithromycin in treatment of systemic infection and septic arthritis induced by type IV group B Streptococcus strain in mice: comparative study with erythromycin and penicillin G. Antimicrob Agents Chemother 39: 1938–47PubMedGoogle Scholar
  34. 34.
    Carevic O, Djokic S (1988) Comparative studies on the effects of erythromycin A and azithromycin upon extracellular release of lysosomal enzymes in inflammatory processes. Agents Actions 25: 124–31CrossRefPubMedGoogle Scholar
  35. 35.
    Mikasa K, Kita E, Sawaki M, Kunimatsu M, Hamada K, Konishi M, Kashiba S, Narita N (1992) The anti-inflammatory effect of erythromycin in zymosan-induced peritonitis of mice. J Antimicrob Chemother 30: 339–48PubMedGoogle Scholar
  36. 36.
    Kadota J, Sakito O, Kohno S, Sawa H, Mukae H, Oda H, Kawakami K, Fukushima K, Hiratani K, Hara K (1993) A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis 147: 153–9PubMedGoogle Scholar
  37. 37.
    Takizawa H, Desaki M, Ohtoshi T, Kawasaki S, Kohyama T, Sato M, Tanaka M, Kasama T, Kobayashi K, Nakajima J et al (1997) Erythromycin modulates IL-8 expression in normal and inflamed human bronchial epithelial cells. Am J Respir Crit Care Med 156: 266–71PubMedGoogle Scholar
  38. 38.
    Takizawa H, Desaki M, Ohtoshi T, Kikutani S, Okazaki H, Sato M, Tanaka M, Akiyama N, Shoji S, Hiramatsu K et al (1995) Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells: A potential mechanism of its anti-inflammatory action. Biochem Biophys Res Commun 210: 781–6CrossRefPubMedGoogle Scholar
  39. 39.
    Matsuoka N, Eguchi K, Kawakami A, Tsuboi M, Kawabe Y, Aoyagi T, Nagataki S (1996) Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells. Clin Exp Immunol 104: 501–8CrossRefPubMedGoogle Scholar
  40. 40.
    Saviola G, Abdi Ali L, Rossini P, Campostrini L, Coppini A, Gori M, Ianaro A, Bucci M, de Nucci G, Cirino G (2002) Clarithromycin in rheumatoid arthritis patients not responsive to disease-modifying antirheumatic drugs: an open, uncontrolled pilot study. Clin Exp Rheumatol 20: 373–8PubMedGoogle Scholar
  41. 41.
    Nishimoto N, Sasai M, Shima Y, Nakagawa M, Matsumoto T, Shirai T, Kishimoto T, Yoshizaki K (2000) Improvement in Castleman’s disease by humanized anti-interleukin-6 receptor antibody therapy. Blood 95: 56–61PubMedGoogle Scholar
  42. 42.
    Yoshizaki K, Nishimoto N, Mihara M, Kishimoto T (1998) Therapy of rheumatoid arthritis by blocking IL-6 signal transduction with a humanized anti-IL-6 receptor antibody. Springer Semin Immunopathol 20: 247–59PubMedGoogle Scholar
  43. 43.
    Mahmoud MS, Ishikawa H, Fujii R, Kawano MM (1988) Induction of CD45 Expression and Proliferation in U-266 myeloma cell line by interleukin-6 (IL-6). Blood 92: 3887–97Google Scholar
  44. 44.
    Liu Y, van Kruiningen HJ, West AB, Cartun RW, Cortot A, Colombel JF (1995) Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn’s disease. Gastroenterology 108: 1396–404CrossRefPubMedGoogle Scholar
  45. 45.
    Cartun RW, Van Kruiningen HJ, Pedersen CA, Berman MM (1993) An immunocytochemical search for infectious agents in Crohn’s disease. Mod Pathol 6: 212–19PubMedGoogle Scholar
  46. 46.
    Hermon-Tayler J, Barnes N, Clarke C, Finlayson C (1998) Mycobacterium paratuberculosis cervical lymphadenitis, followed five years later by terminal ileitis similar to Crohn’s disease. Br Med J 316: 449–53Google Scholar
  47. 47.
    Dell’Isola B, Poyart C, Goulet O, Mougenot JF, Sadoun-Journo E, Brousse N, Schmitz J, Ricour C, Berche P (1994) Detection of Mycobacterium paratuberculosis by polymerase chain reaction in children with Crohn’s disease. J Infect Dis 169: 449–51PubMedGoogle Scholar
  48. 48.
    Millar D, Ford J, Sanderson J, Withey S, Tizard M, Doran T, Hermon-Taylor J (1996) IS900 PCR to detect Mycobacterium paratuberculosis in retail supplies of whole pasteurized cows’ milk in England and Wales. Appl Environ Microbiol 62: 3446–52PubMedGoogle Scholar
  49. 49.
    Swift GL, Srivastava ED, Stone R, Pullan RD, Newcombe RG, Rhodes J, Wilkinson S, Rhodes P, Roberts G, Lawrie BW (1994) Controlled trial of anti-tuberculous chemotherapy for two years in Crohn’s disease. Gut 35: 363–8PubMedGoogle Scholar
  50. 50.
    Gui GP, Thomas PR, Tizard ML, Lake J, Sanderson JD, Hermon-Taylor J (1997) Two-year-outcomes analysis of Crohn’s disease treated with rifabutin and macrolide antibiotics. J Antimicrob Chemother 39: 393–400CrossRefPubMedGoogle Scholar
  51. 51.
    Day R, Forbes A (1999) Heparin, cell adhesion, and pathogenesis of inflammatory bowel disease. Lancet 354: 62–5CrossRefPubMedGoogle Scholar
  52. 52.
    Day R, Ilyas M, Daszak P, Talbot I, Forbes A (1999) Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy. Dig Dis Sci 44: 2508–15CrossRefPubMedGoogle Scholar
  53. 53.
    Colgan SP, Comerford KM, Lawrence DW (2002) Epithelial cell-neutrophil interactions in the alimentary tract: a complex dialog in mucosal surveillance and inflammation. The Scientific World Journal 2: 76–88Google Scholar
  54. 54.
    Tanabe H, Yokota K, Kohgo Y (1999) Localization of syndecan-1 in human gastric mucosa associated with ulceration. J Pathol 187: 338–44CrossRefPubMedGoogle Scholar
  55. 55.
    Kuzin II, Snyder JE, Ugine GD, Wu D, Lee S, Bushnell T Jr, Insel RA, Young MF, Bottaro A (2001) Tetracyclines inhibit activated B cell function. Int Immunol 12: 921–931CrossRefGoogle Scholar
  56. 56.
    Amin AR, Attur MG, Thakker GD, Patel PD, Vyas PR, Patel RN, Patel IR, Abramson SB (1996) A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci USA 93: 14014–19CrossRefPubMedGoogle Scholar
  57. 57.
    Amin AR, Patel RN, Thakker GD, Lowenstein CJ, Attur MG, Abramson SB (1997) Post-transcriptional regulation of inducible nitric oxide synthase mRNA in murine macrophages by doxycycline and chemically modified tetracyclines. FEBS Lett 410:259–64CrossRefPubMedGoogle Scholar
  58. 58.
    Pruzanski W, Greenwald RA, Street IP, Laliberte F, Stefanski E, Vadas P (1992) Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline. Biochem Pharmacol 44: 1165–70CrossRefPubMedGoogle Scholar
  59. 59.
    Shapira L, Soskolne WA, Houri Y, Barak V, Halabi A, Stabholz A (1996) Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. Infect Immun 64: 825–8PubMedGoogle Scholar
  60. 60.
    Liu J, Kuszynski CA, Baxter BT (1999) Doxycycline induces Fas/Fas ligand-mediated apoptosis in Jurkat T lymphocytes. Biochem Biophys Res Commun 260: 562–7CrossRefPubMedGoogle Scholar
  61. 61.
    Vernillo AT, Rifkin BR (1998) Effects of tetracyclines on bone metabolism. Adv Dental Res 12: 56–62Google Scholar
  62. 62.
    Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T (1998) Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dental Res 12: 12–6Google Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2005

Authors and Affiliations

  • Keiichi Mikasa
    • 1
  • Kei Kasahara
    • 2
  • Eiji Kita
    • 3
  1. 1.Center for Infectious DiseasesNara Medical UniversityNaraJapan
  2. 2.Department of Medicine IINara Medical UniversityNaraJapan
  3. 3.Department of BacteriologyNara Medical UniversityNaraJapan

Personalised recommendations