ab21403

Different monocyte reaction patterns in newly diagnosed, untreated rheumatoid arthritis and lupus patients probably confer disparate C-reactive protein levels

L.-B. Liou

Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-yuan County, Taiwan

ABSTRACT
Objectives
To investigate the different capacities of monocytes to produce cytokines in newly diagnosed, untreated patients with rheumatoid arthritis (RA) or systemic lupus and to examine the possible correlation among serum C-reactive protein (CRP), cytokines, swollen joint counts, and erythrocyte sedimentation rates (ESR) in untreated RA patients.

Methods
Monocytes from untreated RA or lupus patients were cultured in vitro with lipopolysaccharide (LPS, as bacterial infection) or immune complexes (as endogenous immune deviation) and supernatants were collected for cytokine determination. Sera from RA patients were assayed for interleukin-6 (IL-6), IL-1b, IL-10, tumor necrosis factor-alpha (TNF-a) and IL-1 receptor antagonist (IL-1ra). These cytokines were related to serum CRP, swollen joint counts, and ESR.

Results
RA monocytes uniformly produced IL-6, IL-1b, TNF-a, or IL-10 in vitro. In contrast, lupus monocytes could be divided into two subsets: (i) monocytes which produce cytokines on LPS stimulation but not on challenging with immune complexes; and (ii) monocytes which, interestingly, generate cytokines on stimulation by immune complexes but not LPS. These cytokines in turn stimulate the liver to synthesize CRP differently in the SLE subsets and RA patients. Moreover, serum IL-1ra levels correlated significantly with serum IL-6, IL-1b, and TNF-a concentrations (p = 0.005, 0.008, or 0.040, respectively), but not with IL-10 (p = 0.582) in RA patients.

Conclusions
Two lupus subsets exist that react either to LPS or immune complexes to produce CRP-inducing cytokines, in contrast to homogeneous RA monocytes. This is the first report that different reaction patterns of CRP-inducing cytokine production in RA and lupus monocytes probably underlie the high CRP levels in RA versus low heterogeneity in lupus. The correlation of serum IL-1ra levels with serum IL-6, IL-1b, or TNF-a concentrations, and the borderline correlation of the former with CRP levels, demonstrate that IL-1ra is an acute phase reactant in RA as well as in SLE patients.

Key words
Untreated rheumatoid arthritis and untreated lupus, monocytes, in vitro cytokines, C reactive protein.

This study was supported by research grants from Chang Gung Memorial Hospital, Taipei, Taiwan (CMRP 529 and 1022).
Please address correspondence and reprint requests to: Lieh-bang Liou, MD, PhD, Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 5 Fu-shin St, Kwei-san Hsiang, Tao-yuan County, Taiwan 333.
E-mail: b890121@adm.cgmh.org.tw