Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM)

Ashutosh K. Mangalam, Amita Aggarwal, Sita Naik

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


GSTM has been used for long in the treatment of rheumatoid arthritis (RA). However, its mechanism of action is still poorly understood. In the last decade, tumor necrosis factor-α (TNF-α) has emerged as the major pro-inflammatory cytokine in the pathogenesis of RA. We studied the effect of GSTM on spontaneous and LPS-stimulated TNF-α production by human peripheral blood mononuclear cells (PBMCs) of normal volunteers. PBMCs were isolated from 20 normal volunteers and cultured in the presence or absence of lipopolysaccharide (LPS 10 ng/ml) and GSTM (1 μg/ml). TNF-α level was measured using commercial enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). The TNF-α response to LPS was heterogeneous. PBMCs of 24 subjects showed high LPS-stimulated TNF-α production (LPS-responsive group), whereas that of six individuals had low LPS-stimulated TNF-α production (LPS-non-responsive group). GSTM-stimulated spontaneous TNF-α production and inhibited LPS-stimulated TNF-α production in 16 of 24 (75%) individuals of LPS-responsive group and one of six individuals (17%) of LPS-non-responsive group. The suppression of TNF-α by GSTM was also demonstrated at the mRNA level. We conclude that there is a heterogeneity among normal population for TNF-α production in response to LPS, and GSTM inhibits LPS-stimulated TNF-α production, primarily in LPS responders. Further study is needed to establish the relationship between LPS responsiveness and GSTM suppression.

Original languageEnglish (US)
Pages (from-to)1165-1172
Number of pages8
JournalInternational Immunopharmacology
Issue number6
StatePublished - Jun 2001


  • Cytokines
  • Gold compounds
  • Rheumatoid arthritis
  • Sodium aurothiomalate
  • Tumor necrosis factor (TNF)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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