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Anti-inflammatory and anti-itch activity of sertaconazole nitrate

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Abstract

Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.

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Abbreviations

PHA:

Phytohemagglutinin

PBMC:

Peripheral blood mononuclear cells

RTX:

Resiniferatoxin

TPA:

Tetradecanoyl phorbol acetate

TNFα:

Tumor necrosis factor-α

IL-2:

Interleukin-2

IFNγ:

Interferon γ

IL-4:

Interleukin-4

GM-CSF:

Granulocyte macrophage colony-stimulating factor

References

  1. Agut J, Tarrida N, Sacristan A, Ortiz JA (1996) Antiinflammatory activity of topically applied sertaconazole nitrate. Meth Find Exp Clin Pharmacol 18:233–234

    CAS  Google Scholar 

  2. Al Hasan M, Fitzgerald SM, Saoudian M, Krishnaswanmy G (2004) Dermatology for the practicing allergist: tinea pedis and its complications. Clin Mol Allergy 2:5

    Article  PubMed  Google Scholar 

  3. Anderson MR, Klink K, Cohrssen A (2004) Evaluation of vaginal complaints. JAMA 291:1368–1379

    Article  PubMed  CAS  Google Scholar 

  4. Andoh T, Kuraishi Y (2003) Nitric oxide enhances substance P-induced itch-associated responses in mice. Br J Pharmacol 138:202–208

    Article  PubMed  CAS  Google Scholar 

  5. Aste N, Pau M, Aste N, Biggio P (2003) Tinea pedis observed in Cagliari, Italy, between 1996 and 2000. Mycoses 46:38–41

    Article  PubMed  CAS  Google Scholar 

  6. Barkey WF (1987) Striae and persistent tinea corporis related to prolonged use of betamethasone dipropionate 0.05% cream/clotrimazole 1% cream (Lotrisone cream). J Am Acad Dermatol 17:518–519

    Article  PubMed  CAS  Google Scholar 

  7. Bernhard JD (1994) Scratching. In: Bernhard JD (ed) Itch mechanisms and management of pruritus. McGraw-Hill, New York, pp 90–103

    Google Scholar 

  8. Carrillo-Munoz AJ, Fernandez-Torres B, Guarro J (2003) In vitro antifungal activity of sertaconazole against 309 dermatophyte clinical isolates. J Chemother 15:555–557

    PubMed  CAS  Google Scholar 

  9. Carrillo-Munoz AJ, Guglietta A, Palacin C et al (2004) In vitro antifungal activity of sertaconazole compared with nine other drugs against 250 clinical isolates of dermatophytes and Scopulariopsis brevicaulis. Chemotherapy 50:308–313

    Article  PubMed  CAS  Google Scholar 

  10. Cohen AD, Wolak A, Alkan M, Shalev R, Vardy DA (2002) AFSS: athlete’s foot severity score. A proposal and validation. Mycoses 45:97–100

    Article  PubMed  CAS  Google Scholar 

  11. De Jager W, te Velthuis H, Prakken BJ, Kuis W, Rijkers GT (2003) Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells. Clin Diagn Lab Immunol 10:133–139

    Article  PubMed  CAS  Google Scholar 

  12. Engeman T, Gorbachev AV, Kish DD, Fairchild RL (2004) The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites. J Leukoc Biol 76:941–949

    Article  PubMed  CAS  Google Scholar 

  13. Erbagci Z (2004) Topical therapy for dermatophytoses: should corticosteroids be included? Am J Clin Dermatol 5:375–384

    Article  PubMed  Google Scholar 

  14. Friccius H, Pohla H, Adibzadeh M, Siegels-Hubenthal P, Schenk A, Pawelec G (1992) The effects of the anti-fungal azoles itraconazole, fluconazole, ketoconazole and miconazole on cytokine gene expression in human lymphoid cells. Int J Immunopharmacol 14:791–799

    Article  PubMed  CAS  Google Scholar 

  15. Holzer P (1998) Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol 30:5–11

    PubMed  CAS  Google Scholar 

  16. Koga T, Ishizaki H, Matsumoto T, Hori Y (1993) Cytokine production of peripheral blood mononuclear cells in a dermatophytosis patient in response to stimulation with trichophytin. J Dermatol 20:441–443

    PubMed  CAS  Google Scholar 

  17. Koga T, Shimizu A, Nakayama J (2001) Interferon-gamma production in peripheral lymphocytes of patients with tinea pedis: comparison of patients with and without tinea unguium. Med Mycol 39:87–90

    Article  PubMed  CAS  Google Scholar 

  18. Kuraishi Y, Nagasawa T, Hayashi K, Satoh M (1995) Scratching behavior induced by pruritogenic but not algesiogenic agents in mice. Eur J Pharmacol 275:229–233

    Article  PubMed  CAS  Google Scholar 

  19. Levitz SM (1992) Overview of host defenses in fungal infections. Clin Infect Dis Suppl 1:S37–S42

    Google Scholar 

  20. Linhares IM, Witkin SS, Miranda SD et al (2001) Differentiation between women with vulvovaginal symptoms who are positive or negative for Candida species by culture. Infect Dis Obstet Gynecol 9:221–225

    Article  PubMed  CAS  Google Scholar 

  21. Merlos M, Vericat ML, Garcia-Rafanell J, Forn J (1996) Topical anti-inflammatory properties of flutrimazole, a new imidazole anti-fungal agent. Inflamm Res 45:20–25

    Article  PubMed  CAS  Google Scholar 

  22. Mertens RL, Morias J, Verhamme G (1976) A double-blind study comparing Daktacort, miconazole and hydrocortisone in inflammatory skin infections. Dermatologica 153:228–235

    Article  PubMed  CAS  Google Scholar 

  23. Moss RB, Moll T, El-Kalay M et al (2004) Th1/Th2 cells in inflammatory disease states: therapeutic implications. Expert Opin Biol Ther 4:1887–1896

    Article  PubMed  CAS  Google Scholar 

  24. Nakajima H (2005) The pathophysiology and defense mechanism against superficial and subcutaneous fungal infection. Nippon Ishinkin Gakkai Zasshi 46:5–9

    PubMed  Google Scholar 

  25. Nakamura Y, Kano R, Hasegawa A, Watanabe S (2002) Interleukin-8 and tumor necrosis factor alpha production in human epidermal keratinocytes induced by Trichophyton mentagrophytes. Clin Diagn Lab Immunol 9:935–937

    Article  PubMed  CAS  Google Scholar 

  26. Palacin C, Tarrago C, Ortiz JA (2000) Sertaconazole: pharmacology of a gynecological antifungal agent. Int J Gynaecol Obstet 71(Suppl 1):S37–S46

    Article  PubMed  CAS  Google Scholar 

  27. Rao TS, Currie JL, Shaffer AF, Isakson PC (1993) Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. Inflammation 17:723–741

    Article  PubMed  CAS  Google Scholar 

  28. Richardson JD, Vasko MR (2002) Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther 302:839–845

    Article  PubMed  CAS  Google Scholar 

  29. Schmelz M, Handwerker HO (2003) Neurophysiologic basis of itch. In: Yosipovitch G, Greaves MW, Fleischer AB, McGlone F (eds) Itch basic mechanisms and therapy. Marcel Dekker, New York, pp 5–20

    Google Scholar 

  30. Slunt JB, Taketomi EA, Woodfolk JA, Hayden ML, Platts-Mills TA (1996) The immune responses to Trichophyton tonsurans: distinct T cell cytokine profiles to a single protein among subjects with immediate and delayed hypersensitivity. J Immunol 157:5192–5197

    PubMed  CAS  Google Scholar 

  31. Steinhilber D, Jaschonek K, Knospe J, Morof O, Roth HJ (1990) Effects of novel anti-fungal azole derivatives on the 5-lipoxygenase and cyclooxygenase pathway. Arzneimittelforschung 40:1260–1263

    PubMed  CAS  Google Scholar 

  32. Szallasi A, Blumberg PM (1989) Neurogenic component of phorbol ester-induced mouse skin inflammation. Cancer Res 49:6052–6057

    PubMed  CAS  Google Scholar 

  33. Torres J, Marquez M, Camps F (2000) Sertaconazole in the treatment of mycoses: from dermatology to gynecology. Int J Gynaecol Obstet 71(Suppl 1):S3-S20

    Article  PubMed  CAS  Google Scholar 

  34. Van Wauwe J, Aerts F, Walter H, de Boer M (1995) Cytokine production by phytohemagglutinin-stimulated human blood cells: effects of corticosteroids, T cell immunosuppressants and phosphodiesterase IV inhibitors. Inflamm Res 44:400–405

    Article  PubMed  Google Scholar 

  35. Weinstein A, Berman B (2002) Topical treatment of common superficial tinea infections. Am Fam Physician 65:2095–2102

    PubMed  Google Scholar 

  36. Woodfolk JA, Platts-Mills TA (2001) Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: delayed-type hypersensitivity-associated major epitopes induced Th1- and Th2-dominated responses. J Immunol 167:5412–5419

    PubMed  CAS  Google Scholar 

  37. Wortzel MH (1982) A double-blind study comparing the superiority of a combination anti-fungal (clotrimazole)/steroidal (betamethasone dipropionate) product. Cutis 30:258–261

    PubMed  CAS  Google Scholar 

  38. Yosipovitch G, Greaves MW (2003) Definitions of itch. In: Yosipovitch G, Greaves MW, Fleischer AB, McGlone F (eds) Itch basic mechanisms and therapy. Marcel Dekker, New York, pp 1–4

    Google Scholar 

  39. Young JM, De Young LM (1989) Cutaneous models of inflammation for the evaluation of topical and systemic pharmacological agents. In: Chang JY, Lewis JA (eds) Pharmacol methods control inflammation. Alan R Liss Inc, New York, pp 215–231

    Google Scholar 

  40. Zhang L, Tinkle SS (2000) Chemical activation of innate and specific immunity in contact dermatitis. J Invest Dermatol 115:168–176

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to Dr. Jeffrey Travers for discussions of the manuscript.

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Authors and Affiliations

  1. Preclinical Pharmacology, Skin Research Center, Johnson and Johnson Consumer Products, 199 Grandview Road, Skillman, NJ, 08558, USA

    Frank Liebel, Peter Lyte, Michelle Garay, Jeffrey Babad & Michael D. Southall

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  1. Frank Liebel
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  2. Peter Lyte
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  3. Michelle Garay
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  4. Jeffrey Babad
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  5. Michael D. Southall
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Correspondence to Michael D. Southall.

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Liebel, F., Lyte, P., Garay, M. et al. Anti-inflammatory and anti-itch activity of sertaconazole nitrate. Arch Dermatol Res 298, 191–199 (2006). https://doi.org/10.1007/s00403-006-0679-8

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  • DOI: https://doi.org/10.1007/s00403-006-0679-8

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