Restoring the balance between pro-inflammatory and anti-inflammatory cytokines in the treatment of rheumatoid arthritis: New insights from animal models

Adrienn Markovics, Ken S. Rosenthal, Katalin Mikecz, Roy E. Carambula, Jason C. Ciemielewski, Daniel H. Zimmerman

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations

Abstract

Rheumatoid arthritis (RA) and other autoimmune inflammatory diseases are examples of imbalances within the immune system (disrupted homeostasis) that arise from the effects of an accumulation of environmental and habitual insults over a lifetime, combined with genetic predispo-sitions. This review compares current immunotherapies—(1) disease-modifying anti-rheumatic drugs (DMARDs) and (2) Janus kinase (JAK) inhibitors (jakinibs)—to a newer approach—(3) therapeutic vaccines (using the LEAPS vaccine approach). The Ligand Epitope Antigen Presentation System (LEAPS) therapies are capable of inhibiting ongoing disease progression in animal models. Whereas DMARDs ablate or inhibit specific proinflammatory cytokines or cells and jakinibs inhibit the receptor activation cascade for expression of proinflammatory cytokines, the LEAPS therapeutic vaccines specifically modulate the ongoing antigen-specific, disease-driving, proinflammatory T memory cell responses. This decreases disease presentation and changes the cytokine conversation to decrease the expression of inflammatory cytokines (IL-17, IL-1(α or β), IL-6, IFN-γ, TNF-α) while increasing the expression of regulatory cytokines (IL-4, IL-10, TGF-β). This review refocuses the purpose of therapy for RA towards rebalancing the immune system rather than compromising specific components to stop disease. This review is intended to be thought provoking and look forward towards new therapeutic modalities rather than present a final definitive report.

Original languageEnglish (US)
Article number44
JournalBiomedicines
Volume10
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

Keywords

  • Aggrecan)
  • Animal models
  • Anti-inflammatory
  • Collagen-induced arthritis
  • Cytokines
  • Immunotherapy
  • Inflammatory
  • PG G1 domain-induced arthritis
  • Peptide vaccine
  • Proteo-glycan (PG
  • Rheuma-toid arthritis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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