Effect of Tacrolimus and Cyclosporine Immunosuppressants on Peripheral Nerve Regeneration: Systematic Review and Meta-analysis

Stéphanie Farias Seixas; Gabriele Carra Forte; Gabriela Agne Magnus; Valentina Stanham; Rita Mattiello; Jefferson Braga Silva

doi:10.1055/s-0041-1736467

Effect of Tacrolimus and Cyclosporine Immunosuppressants on Peripheral Nerve Regeneration: Systematic Review and Meta-analysis

Rev Bras Ortop (Sao Paulo). 2022 May 27;57(2):207-213. doi: 10.1055/s-0041-1736467. eCollection 2022 Apr.

Authors

Stéphanie Farias Seixas¹, Gabriele Carra Forte², Gabriela Agne Magnus³, Valentina Stanham³, Rita Mattiello⁴, Jefferson Braga Silva¹

Affiliations

¹ Serviço de Cirurgia da Mão e Microcirurgia Reconstrutiva, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brasil.
² Departamento de Radiologia, Pontifícia Universidade Católica do Rio Grande do Sul, RS, Brasil.
³ Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS Brasil.
⁴ Programa de Pós-graduação em Pediatria e Saúde da Criança; Programa de Pós-graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brasil.

Abstract

Peripheral nerve damage is an important cause of seeking medical attention. It occurs when the continuity of structures is interrupted and the propagation of nervous impulses is blocked, affecting the functional capacity of individuals. To assess the effects of the immunosuppressants tacrolimus and cyclosporine on the regeneration of peripheral nerves, a systematic review of the literature was carried out. The articles included were published until September 2018 and proposed to evaluate the effects of the immunosuppressants tacrolimus and cyclosporine on nerve regeneration and neuroprotection, available in the MEDLINE, EMBASE, Cochrane Library, Web of Science, Oxford Pain Relief Database, and LILACS databases. The research analysed a total of 56 articles, of which 22 were included in the meta-analysis. Statistical analysis suggests the protective effect of tacrolimus in the regeneration of the number of myelinated axons (95% confidence interval [CI]: 0.93-2.39; p < 0.01); however, such effect was not observed in relation to cyclosporine (95%CI: - 0.38-1.18; p = 0.08) It also suggests that there is a significant relationship between the use of tacrolimus and myelin thickness (95%CI= 2.00-5.71; p < 0. 01). The use of immunosuppressants in the regeneration of peripheral nerve damage promotes an increase in the number of myelinated axons in general, regardless of the administered dose. In addition, it ensures greater myelin thickness, muscle weight and recovery of the sciatic functional index. However, heterogeneity was high in most analyses performed.

Keywords: FK506; cyclosporine; immunosuppressive agents; nerve regeneration; peripheral nerve; tacrolimus.

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