A Humanized Anti-Interleukin 6 Receptor Monoclonal Antibody, Tocilizumab, for the Treatment of Endometriosis in a Rat Model

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Tocilizumab treatment reduced endometriotic implant volume and fibrosis and decreased VEGF in a rat model, suggesting a regressive effect on endometriosis.

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This paper investigated the efficacy of blocking the interleukin-6 (IL-6) pathway using the anti-IL-6 receptor monoclonal antibody tocilizumab in a rat endometriosis model created by peritoneal implantation of autologous endometrial tissue. Twenty-two Wistar female rats were assigned to tocilizumab (8 mg/kg intraperitoneally every 2 weeks) or saline control, and after 4 weeks implant volume, histopathology (including epithelial preservation scoring), fibrosis, and immunohistochemical staining for IL-6 and vascular endothelial growth factor (VEGF) in ectopic and eutopic endometrium were assessed. Tocilizumab was associated with smaller post-treatment lesion volumes, lower histologic and fibrosis scores, and reduced VEGF immunoreactivity, while IL-6 levels and endometrial thickness were similar between groups; the authors did not report additional mechanistic outcomes beyond these measures. This paper is centrally about endometriosis — it evaluates tocilizumab’s anti-IL-6 receptor effects on regression of endometriotic implants in rats.

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Abstract

Objective The aim of this study was to investigate the efficacy of anti-interleukin 6 (IL-6) therapy in the treatment of endometriosis in a rat model. Study Design After the peritoneal implantation of autologous endometrial tissue, 22 Wistar female rats were divided to create 2 intervention groups: the tocilizumab group (n = 13) and the control group (n = 9). After measuring implant volume, saline was administered to the rats in the control group and 8 mg/kg tocilizumab was administered intraperitoneally to the rats in the tocilizumab-treated group every 2 weeks. After a 4-week treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate the preservation of epithelia. Fibrosis score was assessed between the groups. Ectopic and eutopic endometrium were evaluated immunohistochemically for IL-6 and vascular endothelial growth factor (VEGF).

Results

There was a significant difference between the volumes of implants before and after treatment in the tocilizumab group (P < .05). The posttreatment volumes of lesions were smaller in the tocilizumab group than in the control group. Histologic and fibrosis scores were lower in the tocilizumab group than in the control group. Immunoreactivity intensity for VEGF was significantly decreased in the tocilizumab group for ectopic and eutopic endometrium (P < .05). Interleukin 6 levels and endometrial thickness for ectopic and eutopic endometrium were similar between the groups.

Conclusion

Tocilizumab treatment had a regressive effect on the endometriotic implants. Similar content being viewed by others

References

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Sci. 23, 662–669 (2016). https://doi.org/10.1177/1933719115612134 Published: Issue date: DOI: https://doi.org/10.1177/1933719115612134

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Condition tags

endometriosis

MeSH descriptors

Antibodies, Monoclonal, Humanized Disease Models, Animal Endometriosis Endometriosis Receptors, Interleukin-6 Receptors, Interleukin-6 Animals Antibodies, Monoclonal, Humanized Antibodies, Monoclonal, Humanized Endometriosis Endometriosis Female Rats Rats, Wistar Receptors, Interleukin-6

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