Antibiotic effects on phagocyte chemiluminescence in vitro

  • L. A. Pierce
  • W. O. Tarnow-Mordi
  • I. A. Cree


Phagocytes are an essential defence against infection. Since drugs which affect their function may alter the outcome of infections, we have studied the effect of nine antibiotics on phagocyte function in vitro. The effects of antibiotics on the respiratory burst function of phagocytes from healthy adult donors were investigated using lucigenin-enhanced chemiluminescence in response to serum-opsonised zymosan. Aminoglycosides showed dose-dependent suppression of polymorphonuclear leucocyte chemiluminescence, except streptomycin which caused enhancement. Erythromycin caused profound suppression of chemiluminescence from both polymorphonuclear leucocytes and monocytes. Benzylpenicillin and the cephalosporins caused variable suppression of phagocyte chemiluminescence: cefotaxime increased monocyte chemiluminescence in some experiments. None of the drugs produced suppression at clinically relevant plasma concentrations, but erythromycin and some other drugs are preferentially concentrated in phagocytes to levels which suppress their oxidative metabolism in vitro. It is therefore possible that some antibiotics alter phagocyte function: ex vivo studies of phagocyte function in patients taking antibiotics would be valuable.

Key words

Antibiotics Phagocytes Neutrophils Monocytes Chemiluminescence 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Van den Broek PJ. Antimicrobial drugs, microorganisms and phagocytes. Rev Infect Dis 1989; 11:213.PubMedGoogle Scholar
  2. 2.
    Van der Auwera P. The immunomodulating effects of antibiotics. Curr Opin Infect Dis 1988; 1:363.CrossRefGoogle Scholar
  3. 3.
    Blair AL, Cree IA, Beck JS, Hastings MJG. Measurement of phagocyte chemiluminescence in a microtitre plate format. J Immunol Methods 1988; 112:163.PubMedCrossRefGoogle Scholar
  4. 4.
    Blair AL, Cree IA, Beck JS. Measurement of phagocyte chemiluminescence using a microtitre plate luminometer. J Biolumin Chemilumin 1989; 3:67.PubMedCrossRefGoogle Scholar
  5. 5.
    Cree IA. Assays of human phagocyte function using microtitre plate luminometers. In: Stanley PE, Kricka LJ (eds) Bioluminescence and chemiluminescence. Current status. Chichester: Wiley; 1991; 261–264.Google Scholar
  6. 6.
    Dacie JV, Lewis SM. Practical haematology, 6th edn. Edinburgh: Churchill Livingstone, 1984.Google Scholar
  7. 7.
    Lachman PJ, Hobart MJ. Complement technology. In: Weir DM (ed) Handbook of experimental immunology, vol. 3, 3rd edn. Oxford: Blackwell; 1978:9.Google Scholar
  8. 8.
    Ramage L, Blair AL, Cree IA, Dhillon DP. Effect of Salmeterol on polymorphonuclear leukocyte (PMNL) chemiluminescence in vitro. J Biolumin Chemilumin 1993; 8:247.PubMedCrossRefGoogle Scholar
  9. 9.
    Gilman AG, Rall TW, Nies AS, Taylor P. Goodman and Gilman's the pharmacologic basis of therapeutics, 8th edn. New York: Pergamon 1990.Google Scholar
  10. 10.
    Glette J, Solberg CO, Lehmann V. Factors influencing human polymorphonuclear leukocyte chemiluminescence. Acta Pathol Microbiol Immunol Scand 1982; 90:91.Google Scholar
  11. 11.
    McCafferty AC, Cree IA, McMurdo MET. The influence of age and sex on phagocyte chemiluminescence. J Biolumin Chemilumin. In press.Google Scholar
  12. 12.
    Pierce LA, Cree IA, Blair AL, Tarnow-Mordi WO. The effect of aminoglycosides on human polymorpho-nuclear leukocyte (PMNL) chemiluminescnece. In: Stanley PE, Kricka LJ (eds) Bioluminescence and chemiluminescence. Current status, Chichester: Wiley; 1991:317–320.Google Scholar
  13. 13.
    Seklecki MM, Quintiliani R, Maderazo EG. Aminoglycoside antibiotics moderately impair granulocyte function. Antimicrob Agents Chemother 1978; 13:552.PubMedGoogle Scholar
  14. 14.
    Le Moli S, Seminara R, D'Amelio R, Aiuti F. In vitro and in vivo effect of sisomicin and gentamicin on polymorphonuclear chemotaxis and phagocytosis. Int J Immunopharmacol 1983; 5:49.PubMedCrossRefGoogle Scholar
  15. 15.
    Burgaleta C, Moreno T. Effect of beta-lactams and aminoglycosides on human polymorphonuclear leukocytes. J Antimicrob Chemother 1987; 20:529.PubMedCrossRefGoogle Scholar
  16. 16.
    Milatovic D. Antibiotics and phagocytosis. Eur J Clin Microbiol Infect Dis 1983; 2:414.CrossRefGoogle Scholar
  17. 17.
    Hand WL, King-Thompson N, Holman JW. Entry of roxithromycin (RU965), imipenem, cefotaxime, trimethoprim, and metronidazole into human polymorphonuclear leukocytes. Antimicrob Agents Chemother 1987; 31:1553.PubMedGoogle Scholar
  18. 18.
    Pechère J-C. Cefotaxime—recent experiences. Resistance to third generation cephalosporins: the current situation. Infection 1989; 17:333.PubMedCrossRefGoogle Scholar
  19. 19.
    Labro MT, Babin-Chevaye C, Hakim J. Effects of cefotaxime and cefodizime on human granulocyte functions in vitro. J Antimicrob Chemother 1986; 18:233.PubMedCrossRefGoogle Scholar
  20. 20.
    Labro MT, Amit N, Babin-Chevaye C, Hakim J. Cefodizime (HR 221) potentiation of human neutrophil oxygen-independent bactericidal activity. J Antimicrob Chemother 1987; 19:331.PubMedCrossRefGoogle Scholar
  21. 21.
    Welch WD, Davis D, Thrupp LD. Effect of antimicrobial agents on human polymorphonuclear leukocyte microbicidal function. Antimicrob Agents Chemother 1981; 20:15.PubMedGoogle Scholar
  22. 22.
    Labro MT, El Benna J. Effects of anti-infectious agents on polymorphonuclear neutrophils. Eur J Clin Microbiol Infect Dis 1991; 10:124.PubMedCrossRefGoogle Scholar
  23. 23.
    Cuffini AM, Carlone NA, Xerri L, Forno Pizzoglio M. Synergy of ceftazidime and human macrophages on phagocytosis and killing ofStaphylococcus aureus andPseudomonas aeruginosa. J Antimicrob Chemother 1987; 20:261.PubMedCrossRefGoogle Scholar
  24. 24.
    Pallister CJ, Warnock DW. Effect of antimicrobial and antineoplastic drugs alone and in combination on the phagocytic and candidacidal function of human polymorphonuclear leucocytes. J Antimicrob Chemother 1989; 23:87.PubMedCrossRefGoogle Scholar
  25. 25.
    Repo H. Defects in phagocytic functions. Ann Clin Res 1987; 19:263.PubMedGoogle Scholar
  26. 26.
    Tulkens PM. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis 1991; 10:100.PubMedCrossRefGoogle Scholar
  27. 27.
    Pruul H, Wetherall B, McDonald P. In vitro killing of erythromycin-exposed group A streptococci by polymorphonuclear leukocytes. Eur J Clin Microbiol 1986; 5:405.PubMedCrossRefGoogle Scholar
  28. 28.
    Nelson S, Summer WR, Terry PB, Warr GA, Jakab GJ. Erythromycin-induced suppression of pulmonary antibacterial defenses: a potential mechanism of superinfection in the lung. Am Rev Respir Dis 1987; 136:1207.PubMedGoogle Scholar
  29. 29.
    Prokesch RC, Hand WL. Antibiotic entry into human polymorphonuclear leukocytes. Antimicrob Agents Chemother 1982; 21:373.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • L. A. Pierce
    • 1
  • W. O. Tarnow-Mordi
    • 2
  • I. A. Cree
    • 3
  1. 1.Department of Pathology, Ninewells Hospital and Medical SchoolUniversity of DundeeDundeeUK
  2. 2.Department of Child Health, Ninewells Hospital and Medical SchoolUniversity of DundeeDundeeUK
  3. 3.Department of PathologyInstitute of OphthalmologyLondonUK

Personalised recommendations