Agents and Actions

, Volume 38, Supplement 1, pp 85–90 | Cite as

Macrolide antibiotics as antiinflammatory agents: Roxithromycin in an unexpected role

  • C. Agen
  • R. Danesi
  • C. Blandizzi
  • M. Costa
  • B. Stacchini
  • P. Favini
  • M. Del Tacca
Inflammation

Abstract

The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-l-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-l-arginine assay, (2) significant inhibition of λ-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    A. L. Barry, C. Thornsberry and R. N. Jones,In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin and clindamycin, Antimicrob. Agents Chemoter.31, 343–345 (1987).Google Scholar
  2. [2]
    R. A. Young, J. P. Gonzalez and E. M. Sorkin,Roxithromycin: A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs37, 8–41 (1989).PubMedGoogle Scholar
  3. [3]
    T. Tomomasa, T. Kuroume, H. Arai, K. Wakabayashi and Z. Itoh,Erythromycin induces migrating motor complex in human gastrointestinal tract. Dig. Dis. Sci.31, 157–161 (1986).PubMedGoogle Scholar
  4. [4]
    V. Annese, J. Janssens, G. Vantrappen, J. Tack, T. C. Peeters, P. Willemse and E. Van Cutsem,Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination. Gastroenterology102, 823–828 (1992).PubMedGoogle Scholar
  5. [5]
    T. L. Peeters, G. Matthijs, I. Depoortere, T. Cachet, J. Hoogmartens and G. Vantrappen,Erythromycin is a motilin receptor agonist. Am. J. Physiol.257, G470-G474 (1989).PubMedGoogle Scholar
  6. [6]
    G. Plewig and E. Schopf,Anti-inflammatory effects of antimicrobial agents: An in vivo study. J. Invest. Dermatol.65, 532–537 (1975).PubMedGoogle Scholar
  7. [7]
    J. P. Tarayre, M. Aliaga, M. Barbara, G. Villanova, R. Ballester, J. Tisne-Versailles and J. P. Couzinier,Cutaneously applied erythromycin base reduces various types of inflammatory reactions in mouse ear. Int. J. Tissue React.9, 77–85 (1987).PubMedGoogle Scholar
  8. [8]
    T. Barlam and H. C. Neu,In vitro comparison of the activity of RU 28965, a new macrolide, with that of erythromycin against aerobic and anaerobic bacteria. Antimicrob. Agents Chemoter.25, 529–531 (1984).Google Scholar
  9. [9]
    M. Campa, I. Zolfino, S. Senesi, N. Bernardini, R. Danesi, M. Ducci, M. Oleggini, R. Di Stefano, F. Mosca, A. Lazzarini and M. Del Tacca,The penetration of roxithromycin into human skin. J. Antimicrob. Chemoter.26, 87–90 (1990).Google Scholar
  10. [10]
    M. Del Tacca, R. Danesi, N. Bernardini, M. Ducci, I. Zolfino, S. Senesi, E. Panattoni, M. Gabriele, M. Marcucci, A. Lazzarini and M. Campa,Roxithromycin penetration into gingiva and alveolar bone of odontoiatric patients. Chemotherapy36, 332–336 (1990).PubMedGoogle Scholar
  11. [11]
    P. Agache, P. Amblard, G. Moulin, H. Barriere, L. Texier, C. Beylot and H. Bergoend,Roxithromycin in skin and soft tissue infections. J. Antimicrob. Chemother.20 (suppl. B), 153–156 (1987).PubMedGoogle Scholar
  12. [12]
    J. Sasaki,Clinical evaluation of roxithromycin in odontogenic orofacial infections. J. Antimicrob. Chemoter.20 (suppl. B), 167–170 (1987).Google Scholar
  13. [13]
    H. Makino, S. Kuzuna, T. Naka, T. Saijo and Y. Maki,Antiinflammatory, analgesic, and antipyretic activities of methyl-7-butyl-4,5,6,7-tetrahydro-3-methylamino-4-6-dioxo-5-propyl-2H-pyrazolo[3,4-d]pyrimidine-2-carboxilate (AA-2379), a novel non-acidic agent. Agents and Actions25, 385–393 (1988).PubMedGoogle Scholar
  14. [14]
    S. Kumakura, M. Mishima, S. Kobayashi, H. Shirota, S. Abe, K. Yamada and S. Tsurufuji,Inhibitory effect of indomethacin farnesil, a novel antiinflammatory prodrug, on carrageenan-induced inflammation in rats. Agents and Actions29, 286–291 (1990).PubMedGoogle Scholar
  15. [15]
    E. Antunes, M. Mariano, G. Cirino, S. Levi and G. de Nucci,Pharmacological characterization of polycation induced rat hindpaw oedema. Br. J. Pharmacol.101, 986–990 (1990).PubMedGoogle Scholar
  16. [16]
    L. M. Brand, K. L. Skare, M. E. Loomans, H. H. Reller, R. J. Schwen, D. A. Lade, R. L. Bohne, C. S. Maddin, D. P. Moorehead, R. Fanelli, C. Chiabrando, M. G. Castelli and H. H. Tai,Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345. Agents and Actions31, 329–340 (1990).PubMedGoogle Scholar
  17. [17]
    C. J. E. Niemegeers, W. Van Bruggen, F. Awouters and P. A. J. Janssen,The effects of suprofen in rats with implanted cotton pellets. Arzeim.-Forsch. (Drug Res.)25, 1524–1526 (1975).Google Scholar
  18. [18]
    G. A. Higgs, K. G. Mugridge, S. Moncada and J. R. Vane,Inhibition of tissue damage by the arachidonate lipoxygenase inhibitor BW7555c. Proc. Natl. Acad. Sci. USA81, 2890–2892 (1975).Google Scholar
  19. [19]
    A. Kitchen,Methods for the assessment of drug action on cellular accumulation. InAnti-inflammatory Compounds. InClinical Pharmacology, Vol. 9 (Ed. W. R. N. Williamson) pp. 153–191, Marcel Dekker, New York 1987.Google Scholar
  20. [20]
    W. T. Shier and D. J. DuBourdieu,Polycations as prostaglandin synthesis inducers. II. Structure-activity relationships. Prostaglandins31, 1145–1157 (1986).PubMedGoogle Scholar
  21. [21]
    L. Needham, P. G. Hellewell, T. J. Williams and J. L. Gordon,Endothelial functional responses and increased vascular permeability induced by polycations. Lab. Invest.59, 538–548 (1988).PubMedGoogle Scholar
  22. [22]
    L. J. Ignarro, M. E. Gold, G. M. Buga, R. E. Byrns, K. S. Wood, G. Chaudhuri and G. Frank,Basic polyamino acids rich in arginine, lysine or ornithine cause both enhancement of and refractoriness to formation of endothelium-derived nitric oxide in pulmonary artery and vein. Circ. Res.64, 315–329 (1989).PubMedGoogle Scholar
  23. [23]
    C. Vigo, G. P. Lewis and P. J. Piper,Mechanism of inhibition of phospholipase A 2. Biochem. Pharmacol.29, 623–627 (1980).PubMedGoogle Scholar
  24. [24]
    M. Simionescu, N. Simionescu, J. E. Silbert and G. E. Palade,Differential microdomains on the luminal surface of the capillary endothelium. II. Partial characterization of their anionic sites. J. Cell Biol.90, 614–621 (1981).PubMedGoogle Scholar
  25. [25]
    Y. Miyachi, A. Yoshioka, S. Imamura and Y. Niwa,Effect of antibiotics on the generation of reactive oxygen species. J. Invest. Dermatol.86, 449–453 (1986).PubMedGoogle Scholar
  26. [26]
    K. Dalziel, P. J. Dykes and R. Marks,The effects of tetracycline and erythromycin in a model of acne-type inflammation. Br. J. Exp. Path.68, 67–70 (1987).Google Scholar
  27. [27]
    M. T. Labro, J. El Benna and C. Babin-Chevaye,Comparison of the in-vitro effect of several macrolides on the oxidative burst of human neutrophils. J. Antimicrob. Chemother.24, 561–572 (1989).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • C. Agen
    • 1
  • R. Danesi
    • 2
  • C. Blandizzi
    • 1
  • M. Costa
    • 1
  • B. Stacchini
    • 1
  • P. Favini
    • 3
  • M. Del Tacca
    • 1
  1. 1.Instituto di Farmacologia MedicaUniversità di PisaPisaItaly
  2. 2.Scuola Superiore di Studi Universitari e di Perfezionamento S. AnnaPisaItaly
  3. 3.Roussel PharmaMilanoItaly

Personalised recommendations