Abstract

Introduction: A better understanding of psoriasis pathogenesis resulted in significant development of new, effective anti-psoriatic therapies, albeit new treatment options, especially topical ones, are still awaited. In vitro studies have shown that cefazolin, the first-generation cephalosporin, has the properties of a specific inhibitor of several pro-inflammatory cytokines. This study aimed to evaluate the effects of cefazolin in 3D human psoriasis skin model and to assess the efficacy and tolerability of topical cefazolin in comparison to topical hydrocortisone butyrate in the treatment of psoriasis. Material and methods: Commercially available 3D human psoriasis skin model was used to evaluate the effect of cefazolin on psoriasis-related gene expression: human β-defensin 2 (HBD2, DEFB-4A), psoriasin (S100A7) and skin-derived peptidase inhibitor 3 (PI3), as well IL-6 and IL-8 secretion. H&E staining was performed to evaluate tissue morphology. The clinical test was an open-label, comparative, left to right study with an active comparator. Ten adult subjects with psoriasis were asked to apply 5% cefazolin emulsion twice daily on the psoriatic plaques located in extensor area of the right elbow, and 0.1% hydrocortisone butyrate ointment on the same body area on the opposite side. The treatment continued for 7 days. The disease severity was assessed according to the modified PASI (mPASI) and Investigator Global Assessment (IGA). Patients were also asked to rate concomitant subjective symptoms, treatment tolerability and global therapeutic effect. Results: Cefazolin down-regulated gene expression of HBD2 (DEFB-4A) and psoriasin (S100A7) and did not affect PI3. In the tested conditions the drug did not reduce IL-6 and IL-8 secretion. Histological evaluation revealed a slight thinning of the epithelium in tissues treated with cefazolin. In patients, both of the treatments resulted in a significant reduction of psoriatic plaques, although the therapeutic effect was significantly better for hydrocortisone butyrate ointment. Both drugs equally significantly reduced pruritus intensity. The treatment with cefazolin was well tolerated and any significant adverse events were observed. Conclusions: Cefazolin can be considered an interesting therapeutic option as a topical immunomodulatory, anti-inflammatory drug, but its anti-psoriatic properties have to be confirmed in well-designed, prospective and vehicle-controlled studies.

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