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Comparative studies on the effects of erythromycin A and azithromycin upon extracellular release of lysosomal enzymes in inflammatory processes

  • Immunosuppression and Inflammations
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Abstract

In the present studies thein vivo andin vitro effects of erythromycin A and azithromycin, a new type of macrolide (Fig. 2). were investigated upon extracellular release of lysosomal enzymes, β-glucuronidase (β-Gluc) and β-N-acetylglucosaminidase (β-Glm) by using two experimental model systems:in vivo-adjuvant-induced arthritis in rats andin vitro-human polymorphnuclear leucocytes (PMNL) exposed to bovine serum albumin/anti-bovine serum albumin (BSA/anti-BSA), immune complex. Administrations of erythromycin A or azithromycin at doses of 5,10 and 15 mg/kg into rats one day prior and 2, 4, 6, 8 and 10 days after a single subplantar injection of Freund's complete adjuvant significantly (p<0.01) inhibited extracellular release of lysosomal enzymes tested in the synovial fluid of injected left hind paw. These effects were dose-dependent. Further, erythromycin A and azithromycin at concentrations of 10−7 M, 10−6 M and 10−5 significantly (p<0.01) reduced excocytosis of both lysosomal enzymes, β-Gluc and β-Glm from human PMNL initiated by BSA/anti-BSA in a dose-related fashion. However, azithromycin was by fat more effective (p<0.01) in decreasing extracellular release of β-Gluc and β-Glm either in thein vivo orin vitro experiments in comparison with erythromycin A. Appropriate control experiments excluded the possibilities that erythromycin A or azithromycin interfered with activities of lysosomal enzymes or with test reagents. Also, in no instances was there enhanced release of a cytoplasmic enzyme LDH. It seems possible, that erythromycin A and azithromycin interfere with those processes between immunologic reactants and cell surface which provoke extracellular relase of lysosomal enzymes. Also, these macrolides can exert their effects by modifying lysosomal membrane to be less capable of fusing with plasma membrane, and therefore prevent discharge of acid hydrolases in the extracellular space. The differences observed in the effects between erthromycin A and azithromycin may be due to their different structures or different absorption after oral administration. The observations presented are under active investigations in our laboratory.

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Authors and Affiliations

  1. Institute of Public Health, Ŝarengradska 3, 41000, Zagreb, Yugoslavia

    Olga Carević

  2. Research Institute PLIVA, Ive Lole Ribara 89, 41000, Zagreb, Yugoslavia

    Slobodan Djokić

Authors
  1. Olga Carević
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  2. Slobodan Djokić
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Additional information

Azithromycin: N-methyl-11-aza-10-deoxo-10-dihydroerythromycin.

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Carević, O., Djokić, S. Comparative studies on the effects of erythromycin A and azithromycin upon extracellular release of lysosomal enzymes in inflammatory processes. Agents and Actions 25, 124–131 (1988). https://doi.org/10.1007/BF01969103

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  • DOI: https://doi.org/10.1007/BF01969103

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