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

Ashutosh K. Mangalam, Amita Aggarwal, Sita Naik

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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
Volume1
Issue number6
DOIs
StatePublished - Jun 2001
Externally publishedYes

Fingerprint

Gold Sodium Thiomalate
Antirheumatic Agents
Tumor Necrosis Factor-alpha
Blood Cells
Rheumatoid Arthritis
Healthy Volunteers
Reverse Transcription
Lipopolysaccharides
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM). / Mangalam, Ashutosh K.; Aggarwal, Amita; Naik, Sita.

In: International Immunopharmacology, Vol. 1, No. 6, 06.2001, p. 1165-1172.

Research output: Contribution to journalArticle

Mangalam, Ashutosh K. ; Aggarwal, Amita ; Naik, Sita. / Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM). In: International Immunopharmacology. 2001 ; Vol. 1, No. 6. pp. 1165-1172.
@article{d37b72caacc04707bfef57d0c85af761,
title = "Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM)",
abstract = "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.",
keywords = "Cytokines, Gold compounds, Rheumatoid arthritis, Sodium aurothiomalate, Tumor necrosis factor (TNF)",
author = "Mangalam, {Ashutosh K.} and Amita Aggarwal and Sita Naik",
year = "2001",
month = "6",
doi = "10.1016/S1567-5769(01)00050-9",
language = "English (US)",
volume = "1",
pages = "1165--1172",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM)

AU - Mangalam, Ashutosh K.

AU - Aggarwal, Amita

AU - Naik, Sita

PY - 2001/6

Y1 - 2001/6

N2 - 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.

AB - 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.

KW - Cytokines

KW - Gold compounds

KW - Rheumatoid arthritis

KW - Sodium aurothiomalate

KW - Tumor necrosis factor (TNF)

UR - http://www.scopus.com/inward/record.url?scp=0035026621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035026621&partnerID=8YFLogxK

U2 - 10.1016/S1567-5769(01)00050-9

DO - 10.1016/S1567-5769(01)00050-9

M3 - Article

C2 - 11407310

AN - SCOPUS:0035026621

VL - 1

SP - 1165

EP - 1172

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 6

ER -