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 Table of Contents  
OPINION ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 2  |  Page : 191-193

Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs


Department of Microbiology, Al-Shomali General Hospital, Babil, Iraq

Date of Submission03-Feb-2021
Date of Acceptance19-Apr-2021
Date of Web Publication02-Jun-2021

Correspondence Address:
Dr. Falah Hasan Obayes AL-Khikani
Department of Microbiology, Al-Shomali General Hospital, Babil.
Iraq
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.mgmj_59_20

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Keywords: Immunomodulatory drugs, itraconazole, posaconazole, viral infection


How to cite this article:
AL-Khikani FH. Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs. MGM J Med Sci 2021;8:191-3

How to cite this URL:
AL-Khikani FH. Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs. MGM J Med Sci [serial online] 2021 [cited 2021 Sep 20];8:191-3. Available from: http://www.mgmjms.com/text.asp?2021/8/2/191/317451




  Introduction Top


The widespread therapeutic use of azole-based pharmaceutical drugs has given rise to multiple interests, and their research and development have become a very fast creation of a successful spotlight of infinite space.[1],[2] Itraconazole (ITZ) and posaconazole (POS) belonged to triazole, which is a broad-spectrum antifungal agent commonly used to prevent and treat several lung fungal infections and other medically significant fungi that cause superficial, subcutaneous, and systemic infections in humans.[3] These drugs have few side effects compared with other drugs.[4],[5],[6]

Since antifungal drugs are commonly used in patients who are to some extent immunocompromised, it is important to assess the potential effects of these therapies on the immune system.[7],[8],[9] It has been proposed that the efficacy of some antifungal agents may be related to their capacity to induce cytokine production. This also confirmed that some antifungal drugs increase chemokine levels in the supernatants of human mononuclear cell cultures, such as CCL3 and CCL4.[10]

From invasive fungal infection that is treated with POS and has a great role in the treatment of the disease caused by this fungus are include (chromoblastomycosis, mucormycosis candidiasis, fusariosis, mycetoma, cryptococcosis, aspergillosis, and coccidioidomycosis). Also, ITZ drug has a broad range of activity on fungal infections in humans,[11] with rare resistance compared with another antibiotic.[12],[13],[14],[15] Besides the antifungal role of POS and ITZ, they have antiviral efficacy against some viruses by different mechanisms of action.[16]

As shown by both in vitro and in vivo studies, some drugs, especially antibiotics, have direct modulating effects on the immune system, in addition to their antimicrobial acts such as certain antifungal on the activities of animal and human macrophages, monocytes, and neutrophils.[17]

It is also found that ITZ can exert a marked immunomodulatory effect at a serum level of 1 μg/mL (therapeutically achievable concentration), followed by a slight pulmonary immunosuppressive tendency in healthy males BALB/c mice, which suggests an alternative, but unexplored, mechanism of ITZ-mediated immunomodulation.[18]

This lipophilic antifungal drug of POS is absorbed within human cell membranes, including neutrophils and other leukocytes.[19] It concentrates inside dHL-60 cells to high levels.[20] Aftertouch, these cells are capable of transferring POS to A. fumigatus hyphae and exhibit well antifungal activity to A. fumigatus in vitro.

In an IPA neutropenic mouse model, treatment with POS-charged dHL-60 cells resulted in decreased pulmonary fungal burden and even removal of some mice infections. These findings indicate that neutrophils could be an effective mechanism for POS delivery.[21]

A combination of antiviral drugs also has a role in inhibition replication of multiple serotypes of Dengue virus and the related flavivirus Zika virus, lead to reduced viral single-strand RNA replication, and not a translation of the viral genome.[22] Regarding enteroviruses (which are nonenveloped icosahedral RNA viruses) ITZ, identified as an effective inhibitor of EV71 replication in the low micromolar range, also inhibited other enteroviruses, including coxsackievirus B3, coxsackievirus A16, enterovirus 68, and poliovirus 1, the mechanism of action by time-of-addition assay and transient-replicon assay revealed that ITZ targeted a step involved in RNA replication or polyprotein processing, ITZ, and POS may target a specific site(s) in the viral genome.[23]

The different concentrations of POS within the different peripheral blood compartments can in part contribute to the different concentrations of POS found in the plasma. The intracellular absorption of the azoles tends to be passive and dependent upon the composition of the extracellular media. Therefore, the intracellular and consequently the extracellular concentrations would automatically adjust upon reaching multiple body compartments with distinct extracellular media compositions. The intracellular concentration of POS in mononuclear peripheral blood cells and polymorphonuclear neutrophils has been shown to have greatly increased compared with the plasma concentration.[24] High intracellular POS loading may assist the competent phagocytes in their pathogen-killing tasks.[25] ITZ and POS may be promised antiviral therapy to treat some viral infections including those that have no antiviral drugs yet.[26],[27],[28]


  Conclusion Top


From previous studies, ITZ and POS could be effective drugs against many RNA viral infections in multiple mechanisms, including inhibitions of NAADP-stimulated lysosomal calcium release, NPC1 protein function, increase cholesterol level, acidic PH, and stimulating interferon. Because viral infections are common in the world, which is difficult to control, especially RNA viruses with constantly changing, so some studies have conducted a series of experiments on some of the treatments available for re-use to treatment or prevention of viruses.

As it is known, in viral infection, immune system plays a crucial role in viral elimination and body defending, so using an antibiotic that can enhance immune response, activating innate immunity, stimulate pro-inflammatory responses, like ITZ and POS, may be very important to protect from viral invasion.[8] It has strong immunomodulatory characteristics by triggering pro-inflammatory responses; this effect has been associated with protective effects.[8] ITZ and POS act during infection, not only on the pathogen but also on the host. This issue is of particular interest because patients affected by viral infections may be immunocompromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zhang HZ, Gan LL, Wang H, Zhou CH New progress in azole compounds as antimicrobial agents. Mini Rev Med Chem 2017;17:122-66.  Back to cited text no. 1
    
2.
AL-Khikani FH Dermatophytosis a worldwide contiguous fungal infection: Growing challenge and few solutions. Biomed Biotechnol Res J 2020;4:117-22.  Back to cited text no. 2
    
3.
Ami RB, Lewis RE, Kontoyiannis DP Immunopharmacology of modern antifungals. Clin Infect Dis 2008;47:226-35.  Back to cited text no. 3
    
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AL-Khikani FH, Al-Janabi AA Topical amphotericin B formulas: Promising new application. Int J Med Sci Curr Res 2019;2: 187-96.  Back to cited text no. 4
    
5.
AL-Khikani FH Pulmonary mycoses treated by topical amphotericin B. Biomed Biotechnol Res J 2020;4:123-6. doi: 10.4103/bbrj.bbrj_12_20.  Back to cited text no. 5
    
6.
AL-Khikani FH Refractory fungal vaginitis treated by topical amphotericin B. J Med Sci Res 2020;3:22-6.21.  Back to cited text no. 6
    
7.
Steel HC, Tintinger GR, Anderson R Comparison of the anti-inflammatory activities of imidazole antimycotics in relation to molecular structure. Chem Biol Drug Des 2008;72:225-8.  Back to cited text no. 7
    
8.
AL-Khikani FH Amphotericin B as an antiviral drug: Possible efficacy against COVID-19. Ann Thorac Med 2020;15:118-24.  Back to cited text no. 8
    
9.
Almosawey HA, AL-Khikani FH, Hameed RM, Abdullah YJ, Al-Ibraheemi MK, Al-Asadi AA Tamoxifen from chemotherapy to antiviral drug: Possible activity against COVID-19. Biomed Biotechnol Res J 2020;4:108-16.  Back to cited text no. 9
    
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Fidan I, Yuksel S, Imir T, Kalkanci A, Kustimur S, Ilhan MN The effects of fluconazole and cytokines on human mononuclear cells. Mem Inst Oswaldo Cruz 2007;102:127-31.  Back to cited text no. 10
    
11.
Warnock DW, Campbell CK Medical mycology. Mycol Res 1996;100:1153-62.  Back to cited text no. 11
    
12.
AL-Khikani FH, Abadi RM, Ayit AS Emerging carbapenemase Klebsiella oxytoca with multidrug resistance implicated in urinary tract infection. Biomed Biotechnol Res J 2020;4:148-51. doi: 10.4103/bbrj.bbrj_165_19  Back to cited text no. 12
    
13.
AL-Khikani FH, Auda GA, Ayit AS Correlation study between urinary tract bacterial infection and some acute inflammatory responses. Biomed Biotechnol Res J 2019;3:236-9.  Back to cited text no. 13
    
14.
AL-Khikani FH, Almosawey HAS Be conscious to be healthy: An initiative to prevent recurrent urinary tract infection in Iraqi women. Hamdan Med J 2020;10.4103/HMJ.HMJ_15_20.  Back to cited text no. 14
    
15.
AL-Khikani FH The forgotten role of methenamine to prevent recurrent urinary tract infection: Urgency for reuse 100 years after discovery. Pharma Biomed Res 2020;6:13-6.  Back to cited text no. 15
    
16.
AL-Khikani FH, Hameed RM COVID-19 treatment: Possible role of itraconazole as a new therapeutic option. Int J Health Allied Sci 2020;9:101-3.  Back to cited text no. 16
    
17.
Choi JH, Kwon EY, Park CM, Choi SM, Lee DG, Yoo JH, et al. Immunomodulatory effects of antifungal agents on the response of human monocytic cells to aspergillus fumigatus conidia. Med Mycol 2010;48:704-9.  Back to cited text no. 17
    
18.
Naranjo TW, Lopera D, Zuluaga AF, Cano LE Immunomodulatory activity of itraconazole in lung. Trop J Pharm Res 2016;15:2603-9.  Back to cited text no. 18
    
19.
Taccone FS, Van den Abeele AM, Bulpa P, Misset B, Meersseman W, Cardoso T, et al; AspICU Study Investigators. Epidemiology of invasive aspergillosis in critically ill patients: Clinical presentation, underlying conditions, and outcomes. Crit Care 2015;19:7.  Back to cited text no. 19
    
20.
Campoli P, Al Abdallah Q, Robitaille R, Solis NV, Fielhaber JA, Kristof AS, et al. Concentration of antifungal agents within host cell membranes: A new paradigm governing the efficacy of prophylaxis. Antimicrob Agents Chemother 2011;55:5732-9.  Back to cited text no. 20
    
21.
Baistrocchi SR, Lee MJ, Lehoux M, Ralph B, Snarr BD, Robitaille R, et al. Posaconazole-loaded leukocytes as a novel treatment strategy targeting invasive pulmonary aspergillosis. J Infect Dis 2017;215:1734-41.  Back to cited text no. 21
    
22.
Meutiawati F, Bezemer B, Strating JRM, Overheul GJ, Žusinaite E, Kuppeveld FJM, et al. Posaconazole inhibits dengue virus replication by targeting oxysterol-binding protein. Antiviral Res 2018;157:68-79.  Back to cited text no. 22
    
23.
Gao Q, Yuan S, Zhang C, Wang Y, Wang Y, He G, et al. Discovery of itraconazole with broad-spectrum in vitro antienterovirus activity that targets nonstructural protein 3A. Antimicrob Agents Chemother 2015;59:2654-65.  Back to cited text no. 23
    
24.
Minoprio P Parasite polyclonal activators: New targets for vaccination approaches? Int J Parasitol 2001;3:588-91. doi: 10.1016/s0020-7519(01)00171-0.  Back to cited text no. 24
    
25.
Farowski F, Cornely OA, Vehreschild JJ, Hartmann P, Bauer T, Steinbach A, et al. Quantitation of azoles and echinocandins in compartments of peripheral blood by liquid chromatography-tandem mass spectrometry. Antimicrob Agents Chemother 2010;54:1815-9.  Back to cited text no. 25
    
26.
AL-Khikani FO Surveillance 2019 novel coronavirus (COVID-19) spreading: Is a terrifying pandemic outbreak is soon? Biomed Biotechnol Res J 2020;4:81-2.  Back to cited text no. 26
    
27.
AL-Khikani FH, Kadim BJ, Ayit AS, Abidalali MH Evaluation of cephalosporins resistance in pathogenic bacteria isolated clinically. World News of Natural Sciences 2020;31;110-9.  Back to cited text no. 27
    
28.
AL-Khikani FH The role of blood group in COVID-19 infection: More information is needed. J Nat Sci Med 2020;3:225-56.  Back to cited text no. 28
    




 

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