Pro-Inflammatory Signaling in Dermal Fibroblasts - A Possible Role of Different Botulinum Toxin Formulations - IL-6 Expression

Sep 28, 2026

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Botulinum toxin type A (BoNT-A) formulations are widely used in aesthetic and therapeutic dermatology, yet their immunomodulatory and pro-inflammatory behavior is not fully defined for dermal fibroblasts. This in vitro study compared three commercial BoNT-A formulations (Bocouture, Vistabex, Azzalure) for effects on interleukin-6 (IL-6) at 24, 48, and 72 hours. IL-6 was quantified by ELISA, while viability was assessed by MTT to rule out cytotoxicity. Vistabex increased IL-6 at multiple time points, whereas Bocouture and Azzalure showed no significant IL-6 changes and no relevant viability loss below 80%.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Background and Aims

Patients/Methods and Measurements

Results and Conclusions

Introduction

Cytokine roles and IL-6 function

Journal of Cosmetic Dermatology ORIGINAL ARTICLE OPEN ACCESS Pro-Inflammatory Signaling in Dermal Fibroblasts: A Possible Role of Different Botulinum Toxin Formulationson IL-6 Expression Sabrina Sommatis1 | Roberto Mocchi1 | Serena Di Francesco1 | Stefano Bighetti2 | Luca Bettolini2 | Andrea Carugno3 | Giovanni Paolino4,5 | Mariateresa Rossi2 | Stefania Guida4,5 | Mario Valenti6,7 | Nicola Zerbinati8 1UB-CARE S.R.L.-Spin-Off, University of Pavia, Pavia, Italy | 2Dermatology Department, University of Brescia, Brescia, Italy | 3Department of Medicine and Surgery, University of Insubria, Varese, Italy | 4Dermatology Unit, Università Vita-Salute San Raffaele, Milan, Italy | 5Dermatology Clinic, IRCCS San Raffaele Scientific Institute, Milan, Italy | 6Dermatology Unit, IRCCS Humanitas Research Hospital, Milan, Italy | 7Department of Biomedical Sciences, Humanitas University, Milan, Italy | 8University of Insubria, Department of Medicine and Technology Innovation, Varese, Italy Correspondence: Stefano Bighetti ([s.bighetti@unibs.it](s.bighetti@unibs.it)) Received: 21 May 2025 | Revised: 11 July 2025 | Accepted: 22 December 2025 Keywords: BoNT-A formulations | botulinum toxin type A | complexing proteins | dermal fibroblasts | interleukin-6 (IL-6) | pro-inflammatory cytokines ABSTRACT Background: Botulinum toxin type A (BoNT-A) formulations are extensively employed in aesthetic and therapeutic dermatology. However, their immunomodulatory and pro-inflammatory properties remain incompletely characterized, particularly concerning dermal fibroblasts. Aims: This study aimed to evaluate and compare the effects of three commercially available BoNT-A formulations—Bocouture, Vistabex, and Azzalure—on the expression of interleukin-6 (IL-6), a key pro-inflammatory cytokine, in cultured adult human dermal fibroblasts. Patients/Methods: Human dermal fibroblasts were cultured in vitro and treated with increasing concentrations of Bocouture, Vistabex, and Azzalure. IL-6 expression was measured at 24, 48, and 72 h posttreatment using an enzyme-linked immunosorbent assay (ELISA). Cell viability was assessed by MTT assay to exclude cytotoxic effects. Each condition was tested in triplicate. Data were analyzed using one-way ANOVA with Bonferroni's multiple comparisons posttest. Results: Vistabex significantly increased IL-6 expression at multiple time points, with the most marked elevation observed at 0.5 U/mL after 24 h (p ≤0.0001) . Conversely, Bocouture and Azzalure did not induce significant changes in IL-6 levels across all tested concentrations and time intervals. No formulation reduced fibroblast viability below 80%, confirming the absence of relevant cytotoxicity. Conclusions: These findings suggest a formulation-specific inflammatory response to BoNT-A in dermal fibroblasts, with Vistabex eliciting a notable upregulation of IL-6. The observed differences may be attributed to distinct structural or excipientrelated properties and warrant further investigation to clarify their clinical implications, especially in patients with a predisposition to inflammatory skin responses. 1 | Introduction Cytokines are small proteins (5–20 kDa) that play an important role in the immune system: in particular, they are able to influence the activation, maturation, growth, and differentiation of several cell populations. Within the large cytokines'family, interleukin (IL-) 6 plays a crucial role in inflammatory response by representing one of the main acute phase proteins This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC. Journal of Cosmetic Dermatology, 2026; 25:e70646 1 of 8 [https://doi.org/10.1111/jocd.70646](https://doi.org/10.1111/jocd.70646) and promoting inflammation i

FAQs

Which BoNT-A formulations were compared in the study?

The study evaluated three commercially available BoNT-A formulations: Bocouture, Vistabex, and Azzalure.

How was IL-6 expression measured after treatment?

IL-6 expression in cultured dermal fibroblasts was measured at 24, 48, and 72 hours using an enzyme-linked immunosorbent assay (ELISA).

Did any formulation reduce dermal fibroblast viability?

No. Cell viability remained above 80% for all formulations, indicating no relevant cytotoxic effects under the tested conditions.

Sep 28, 2026

Uploaded by Aria