Mononuclear cell response to lipopolysaccharide in patients with rheumatoid arthritis: relationship with tristetraprolin expression.

Abstract

OBJECTIVE:

To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA).

METHODS:

TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients.

RESULTS:

Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs.

CONCLUSION:

The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.

• Authors: Martina Fabris, Barbara Tolusso, Emma Di Poi, Paola Tomietto, Stefania Sacco, Elisa Gremese, Gianfranco Ferraccioli
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 32 Issue 6 Pg. 998-1005 (Jun 2005) ISSN: 0315-162X [Print] Canada
• PMID: 15940758 (Publication Type: Journal Article)

Chemical References

• Antirheumatic Agents
• DNA-Binding Proteins
• Immediate-Early Proteins
• Lipopolysaccharides
• RNA, Messenger
• Receptors, Tumor Necrosis Factor, Type II
• Tristetraprolin
• Tumor Necrosis Factor-alpha
• ZFP36 protein, human

Topics

• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (immunology)
• Cells, Cultured
• DNA-Binding Proteins (biosynthesis, genetics)
• Female
• Gene Expression
• Humans
• Immediate-Early Proteins (biosynthesis, genetics)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lipopolysaccharides (pharmacology)
• Male
• Middle Aged
• Prognosis
• RNA, Messenger (metabolism)
• Receptors, Tumor Necrosis Factor, Type II (blood, metabolism)
• Time Factors
• Tristetraprolin
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)
• Zinc Fingers (genetics)