THE EFFECT OF FLUCONAZOLE AND AMPHOTERICIN B ON MACROPHAGE FUNCTIONS
Background: Different antimicrobial drugs inhibit functions of the microbial cells but, unfortunately, some of these drugs can also affect the host cells, including macrophages. Since these cells represent the baseline defense against microbial agents, it is important that they are fully activated.
Materials and Methods: In the present study we investigated the effect of amphotericin B and fluconazole on the functions of peritoneal macrophages from Balb/c mice treated with these antimycotics. For each antimycotic the therapeutic dose used in clinical practice (calculated on the mouse body weight) and two-fold higher doses were administered intraperitoneally once a day for three consecutive days. The control group was treated with saline in the same way. Four different tests, candidacidal assay, nitroblue tetrazolium test, adherence capability and phagocytic capability, were used to determine macrophage functions.
Results: Our results confirmed positive effect of high dose amphotericin B on phagocytic capability (31.004.46 %), metabolic changes (27.936.63 %) and adherence capacity (59.248.67 %). Lower doses of drug amphotericin B (2 mg/kg) significantly increased the adherence index of macrophages (71.995.55 %) and intensity of the NBT intracellular reduction (30.203.83 %). Maximum dose of fluconazole expressed significantly higher phagocytic index (30.772.17 %), metabolic changes (24.004.07 %) and candidacidal activities (27.736.73 %), while lower doses of fluconazole (15 mg/kg) significantly increased the adherence index of macrophages (75.585.47 %) as well as the phagocytic index (29.232.40 %). Other results were similar as in control group.
Conclusion: Positive immunomodulatory effects of fluconazole and amphotericin B may be clinically relevant especially in compromised patients who are predisposed to opportunistic fungal infections and require a long-term antimycotic therapy. Synergistic action of macrophages and antimycotics can influence the course of disorders related to immune suppression.
Key words: Amphotericin B, fluconazole, macrophage functions
Dineshshankar J, Sivakumar M, Karthikeyan M, Udayakumar P, Shanmugam KT, Kesavan G.. Immunology of oral candidiasis. J Pharm Bioallied Sci. 2014;6 (suppl 1): 9-12.
Loo DS. Systemic antifungal agents: an update of established and new therapies. Adv Dermatol. 2006; 22:101-24.
Tuzun Y, Kalayciyan A, Engin B, Tuzun B. Life-threathing disorders of mucous membranes. Clinics Dermat. 2005;23(3): 267-75.
Perfect JR, Hachem R,Wingard JR. Update on epidemiology of and preventive strategies for invasive fungal infections in cancer patients. Clin Infect Dis. 2014; 59 (suppl 5): 352-5.
Sims CR, Ostrosky-Zeinchenr L, Rex JH: Invasive candidiasis in immunocompromised hospitalized patients. Arch Med Res. 2005; 36(6): 660-71.
Ahmad I, Owais M, Shahid M et al. Combating fungal infections, Problems and remedy. 1 st ed. Springer, 2010.
Glocker E, Grimbacher B. Chronic mucocutaneous candidiasis and congenital susceptibility to Candida. Curr Opin Allergy Clin Immunol. 2010; 10(6): 542-50.
Fidel PL Jr: Immunity to Candida. Oral Dis. 2002; 8 (suppl 2): 69-75.
Hume DA: The mononuclear phagocyte system. Curr Opin Immunolog. 2006; 18(1): 49-53.
Lionakis MS. New insights into innate immune control of systemic candidiasis. Med Mycol. 2014; 52(6): 555-64.
Kitahara N, Morisaka H, Aoki W et al. Description of the interaction between Candida albicans and macrophages by mixed and quantitative proteome analysis without isolation. AMB Express. 2015; 5(1): 127.
Miyazaki TI, Kohno S. Current recommendations and importance of antifungal stewardship for the management of invasive candidiasis. Expert Rev Anti Infect Ther. 2015; 13(9):1171-83.
Musiol R, Mrozek-Wilczkiewicz A, Polanski J. Synergy against fungal pathogens: Working together is better than working alon. Curr Med Chem. 2014; 21(7): 870-93.
DiDomenico B: Novel antifungal drugs. Curr Opin Microbiol. 1999; 2(5): 509-15.
Varlam DE, Siddiq MM, Parton LA, Russmann H. Apoptosis contributes to amphotericin B-induced nephrotoxicity. Antimicrob Agents Chemother. 2001; 45(3): 679-85.
Yu S, Chai X, Wang Y, et al. Triazole derivatives with improved in vitro antifungal activity over azole drugs. Drug Des Devel Ther. 2014; 8: 383-90.
Dodds ES, Drew RH, Perfect JR: Antifungal Pharmacodynamics: Review of the Literature and Clinical Applications. Pharmacotherapy. 2000; 20(11): 1335-55.
Garcha UK, Brummer E, Stevens DA. Synergy of fluconazole with macrophages for antifungal activity against Candida albicans. Mycopathologia 1995-1996; 132(3): 123-8.
Yamaguchi H, Abe S, Tokuda Y. Immunomodulating activity of antifungal drugs. Ann N Y Acad Sci. 1993; 685: 447-57.
Mesa-Arango AC, Scorzoni L, Zaragoza O. It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug. Front Microbiol. 2012; 3:286. eCollection 2012.
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