# Pro‐Inflammatory Signaling in Dermal Fibroblasts: A Possible Role of Different Botulinum Toxin Formulations on IL‐6 Expression

**Authors:** Sabrina Sommatis, Roberto Mocchi, Serena Di Francesco, Stefano Bighetti, Luca Bettolini, Andrea Carugno, Giovanni Paolino, Mariateresa Rossi, Stefania Guida, Mario Valenti, Nicola Zerbinati

PMC · DOI: 10.1111/jocd.70646 · Journal of Cosmetic Dermatology · 2026-01-02

## TL;DR

The study compares how three botulinum toxin type A formulations affect inflammation in skin cells, finding that one formulation significantly increases a key inflammatory protein.

## Contribution

The study reveals formulation-specific differences in pro-inflammatory responses of dermal fibroblasts to botulinum toxin type A.

## Key findings

- Vistabex significantly increased IL-6 expression in dermal fibroblasts at 0.5 U/mL after 24 hours.
- Bocouture and Azzalure did not significantly alter IL-6 levels across tested concentrations and time points.
- No formulation reduced fibroblast viability below 80%, indicating no relevant cytotoxicity.

## Abstract

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.

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.

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.

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.

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 excipient‐related properties and warrant further investigation to clarify their clinical implications, especially in patients with a predisposition to inflammatory skin responses.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** cytotoxicity (MESH:D064420), Inflammatory (MESH:D007249)
- **Chemicals:** MTT (MESH:C070243)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12759170/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12759170/full.md

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Source: https://tomesphere.com/paper/PMC12759170