Efficacy and safety of 5-aminolevulinic acid in adult-onset Still's disease: A preclinical study in mice and a pilot study in humans

Clin Immunol. 2023 Dec:257:109846. doi: 10.1016/j.clim.2023.109846. Epub 2023 Nov 23.

Abstract

The study aimed to investigate the therapeutic effects of 5-aminolevulinic acid/sodium ferrous citrate (5-ALA/SFC) on adult-onset Still's disease (AOSD), specifically focusing on arthritis and macrophage activation syndrome (MAS). We used mouse models to assess the impact of 5-ALA/SFC on collagen-induced arthritis (CIA) and MAS induced by synthetic oligonucleotides containing CpG motifs (CpG-S-ODN). Additionally, we conducted a pilot study with AOSD patients receiving prednisolone (PSL) treatment and 5-ALA/SFC administration to evaluate its efficacy and safety. The 5-ALA/SFC group exhibited significantly lower joint scores in CIA mice. In CpG-S-ODN-treated mice, 5-ALA/SFC administration led to reduced hemophagocytosis and splenomegaly. The anti-inflammatory properties of 5-ALA/SFC were attributed to the suppression of CCL4 and CXCL10 production in monocytes and the induction of M2 macrophages. AOSD patients treated with 5-ALA/SFC demonstrated successful PSL tapering without adverse events. Collectively, the administration of 5-ALA/SFC showed promising potential in ameliorating arthritis and MAS in AOSD patients.

Keywords: 5-aminolevulinic acid/sodium ferrous citrate; Adult-onset Still's disease; Collagen-induced arthritis; Macrophage activation syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminolevulinic Acid / pharmacology
  • Aminolevulinic Acid / therapeutic use
  • Animals
  • Arthritis*
  • Gene Expression
  • Humans
  • Mice
  • Pilot Projects
  • Still's Disease, Adult-Onset* / drug therapy

Substances

  • Aminolevulinic Acid