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Mononuclear Cell Response to Lipopolysaccharide in Patients with Rheumatoid Arthritis: Relationship with Tristetraprolin Expression
MARTINA FABRIS, BARBARA TOLUSSO, EMMA DI POI, PAOLA TOMIETTO, STEFANIA SACCO, ELISA GREMESE, and GIANFRANCO FERRACCIOLI
ABSTRACT.
Objective. To analyze tumor necrosis factor-a (TNF-a) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA). Methods. TNF-a 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-a mRNA destabilizing factor. TNF receptor p75 (TNFR2) plasma concentrations were also tested in all patients. Results. Controls and patients demonstrated a comparable wide range of TNF-a release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-a release in controls as the cutoff value to distinguish high and low LPS-induced TNF-a-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-a producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-a producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-a 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-a-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs. Conclusion. The LPS-induced TNF-a-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome. (J Rheumatol 2005;32:998-1005) Key Indexing Terms:
LIPOPOLYSACCHARIDE
From the Department of Rheumatology, Universita' Cattolica del Sacro Cuore School of Medicine, Rome; and Rheumatology Unit, Dipartimento Patologia Medicina Sperimentale e Clinica, School of Medicine, University of Udine, Udine, Italy. M. Fabris, BS, Laboratory Staff; B. Tolusso, BS, Laboratory Staff; E. Di Poi, MD; P. Tomietto, MD; S. Sacco, MD; E. Gremese, MD; G.F. Ferraccioli, MD, Professor, Director, Department of Rheumatology, School of Medicine, Universita' Cattolica del Sacro Cuore. Dr. Fabris and Dr. Tolusso contributed equally to this work. Address reprint requests to Dr. G.F. Ferraccioli, Department of Rheumatology, UCSC School of Medicine, Catholic University of Rome, 00168 Rome, Italy. E-mail: gf.ferraccioli@rm.unicatt.it Accepted for publication January 24, 2005. |