Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 Apr;29(4):602–607. doi: 10.1128/aac.29.4.602

Influence of six antifungal agents on the chemiluminescence response of mouse spleen cells.

G K Abruzzo, D M Giltinan, T P Capizzi, R A Fromtling
PMCID: PMC180450  PMID: 3707108

Abstract

The luminol-enhanced chemiluminescence (CL) assay is a measure of the early events of phagocytosis, leukocyte activation, and immune cell interactions. Reduction in the CL response of immune cells may be indicative of an inhibition of the immune response. This study was undertaken to examine the effects of antifungal agents tested at concentrations above and below therapeutically achievable levels on the CL response of mouse spleen cells. The effects of six antifungal agents--amphotericin B, ketoconazole, miconazole, 5-fluorocytosine, Bay-n-7133, and ICI 153,066--were studied. Changes in the CL response were assessed in terms of peak intensity and area under the intensity-time curve compared with appropriate diluent controls for each drug. Only amphotericin B and ketoconazole caused statistically significant lowering of the peak intensity at levels that are therapeutically attainable (mean peak plasma levels of 2 to 4 and 3.5 to 16 micrograms/ml, respectively). Although amphotericin B and ketoconazole caused reduction in the CL response, removal of the unbound drug in the preparation by centrifugation, washing, and suspension of cells in fresh drug-free medium resulted in a return of CL activity equivalent to the activity observed in cells not exposed to these agents. These results suggest that amphotericin B and ketoconazole at therapeutic concentrations may cause a reduction in immune cell antimicrobial activity; the clinical significance of these observations remains to be determined.

Full text

PDF
602

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen R. C., Loose L. D. Phagocytic activation of a luminol-dependent chemiluminescence in rabbit alveolar and peritoneal macrophages. Biochem Biophys Res Commun. 1976 Mar 8;69(1):245–252. doi: 10.1016/s0006-291x(76)80299-9. [DOI] [PubMed] [Google Scholar]
  2. Allen R. C., Stjernholm R. L., Steele R. H. Evidence for the generation of an electronic excitation state(s) in human polymorphonuclear leukocytes and its participation in bactericidal activity. Biochem Biophys Res Commun. 1972 May 26;47(4):679–684. doi: 10.1016/0006-291x(72)90545-1. [DOI] [PubMed] [Google Scholar]
  3. Babior B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978 Mar 23;298(12):659–668. doi: 10.1056/NEJM197803232981205. [DOI] [PubMed] [Google Scholar]
  4. Björkstén B., Ray C., Quie P. G. Inhibition of human neutrophil chemotaxis and chemiluminescence by amphotericin B. Infect Immun. 1976 Jul;14(1):315–317. doi: 10.1128/iai.14.1.315-317.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan C. K., Balish E. Inhibition of granulocyte phagocytosis of Candida albicans by amphotericin B. Can J Microbiol. 1978 Apr;24(4):363–364. doi: 10.1139/m78-061. [DOI] [PubMed] [Google Scholar]
  6. Davies R. R., Zaini F. Antifungal drugs affecting the chemotaxis of polymorphonuclear neutrophils. Sabouraudia. 1985 Apr;23(2):119–123. doi: 10.1080/00362178585380191. [DOI] [PubMed] [Google Scholar]
  7. Fromtling R. A., Shadomy H. J. An overview of macrophage-fungal interactions. Mycopathologia. 1986 Feb;93(2):77–93. doi: 10.1007/BF00437738. [DOI] [PubMed] [Google Scholar]
  8. Giltinan D. M., Capizzi T. P., Abruzzo G. K., Fromtling R. A. Design and analysis considerations in evaluating the chemiluminescence response of mouse spleen cells. J Clin Microbiol. 1986 Mar;23(3):531–535. doi: 10.1128/jcm.23.3.531-535.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marmer D. J., Fields B. T., Jr, France G. L., Steele R. W. Ketoconazole, amphotericin B, and amphotericin B methyl ester: comparative in vitro and in vivo toxicological effects on neutrophil function. Antimicrob Agents Chemother. 1981 Nov;20(5):660–665. doi: 10.1128/aac.20.5.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Martin R. R., Putman M., Greenberg S. B., Wallace R. J., Jr, Wilson S. Z. Serial studies of leukocyte chemiluminescence: lack of effect of macrolide antibiotic therapy. J Med. 1980;11(1):39–48. [PubMed] [Google Scholar]
  11. Milatovic D. Antibiotics and phagocytosis. Eur J Clin Microbiol. 1983 Oct;2(5):414–425. doi: 10.1007/BF02013898. [DOI] [PubMed] [Google Scholar]
  12. Oleske J. M., de la Cruz A., Ahdieh H., Sorvino D., La Braico J., Cooper R., Singh R., Lin R., Minnefor A. Effects of antibiotics on polymorphonuclear leukocyte chemiluminescence and chemotaxis. J Antimicrob Chemother. 1983 Oct;12 (Suppl 100):35–38. doi: 10.1093/jac/12.suppl_c.35. [DOI] [PubMed] [Google Scholar]
  13. Rank E. L., Hopfer R. L., Williams R. P. Amphotericin B causes a decrease in human leukocyte migration. J Antimicrob Chemother. 1981 Dec;8(6):497–500. doi: 10.1093/jac/8.6.497. [DOI] [PubMed] [Google Scholar]
  14. Ritter W., Plempel M. Pharmacokinetics of the oral triazole antimycotic vibunazole in animals. J Antimicrob Chemother. 1984 Sep;14(3):243–252. doi: 10.1093/jac/14.3.243. [DOI] [PubMed] [Google Scholar]
  15. Seklecki M. M., Quintiliani R., Maderazo E. G. Aminoglycoside antibiotics moderately impair granulocyte function. Antimicrob Agents Chemother. 1978 Mar;13(3):552–554. doi: 10.1128/aac.13.3.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Siegel J. P., Remington J. S. Effect of antimicrobial agents on chemiluminescence of human polymorphonuclear leukocytes in response to phagocytosis. J Antimicrob Chemother. 1982 Dec;10(6):505–515. doi: 10.1093/jac/10.6.505. [DOI] [PubMed] [Google Scholar]
  17. Supapidhayakul S. R., Kizlaitis L. R., Andersen B. R. Stimulation of human and canine neutrophil metabolism by amphotericin B. Antimicrob Agents Chemother. 1981 Feb;19(2):284–289. doi: 10.1128/aac.19.2.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tukey J. W., Ciminera J. L., Heyse J. F. Testing the statistical certainty of a response to increasing doses of a drug. Biometrics. 1985 Mar;41(1):295–301. [PubMed] [Google Scholar]
  19. Welch W. D., Davis D., Thrupp L. D. Effect of antimicrobial agents on human polymorphonuclear leukocyte microbicidal function. Antimicrob Agents Chemother. 1981 Jul;20(1):15–20. doi: 10.1128/aac.20.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. van Gulpen C., Kelder O., Mattie H., van der Meer J. W., van't Wout J. Pharmacokinetics of vibunazole (BAY n 7133) administered orally to healthy subjects. J Antimicrob Chemother. 1985 Jul;16(1):75–79. doi: 10.1093/jac/16.1.75. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES