A comparative study of serum and synovial fluid lipoprotein levels in patients with various arthritides
Highlights
► Apolipoproteins, lipoproteins and lipids in synovial fluid of arthritis patients. ► Lipoproteins diffuse into the synovial fluid depending on the degree of inflammation. ► Higher synovial fluid lipid levels in inflammatory arthritis. ► The lipid synovial fluid/serum ratio reflects the synovial permeability. ► The lipid synovial fluid/serum ratio is always lower in osteoarthritis.
Introduction
Inflammatory arthritides, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are associated with multiple alterations in lipid metabolism [1]. It is widely held that acute-phase responses lead to higher serum triglyceride (TG) and lower HDL-cholesterol (HDL-C) concentrations.
Alterations in total cholesterol (TC) and LDL-cholesterol (LDL-C) also seem to occur. The wide range of fluctuations in lipid levels, which are mediated by cytokines, are connected to host defense and tissue repair [2], but when inflammation become chronic these alterations may contribute to the development of cardiovascular disease [3], [4].
It has been postulated that apolipoproteins (apo) and lipoproteins play an important role in modulating both acute and chronic inflammation [5]. HDL, in particular, has an antiinflammatory effect by inhibiting production of pro-inflammatory cytokines induced by T cell contact [6]. At the joint level, inflammation causes increased synovial permeability thereby allowing proteins and lipids to pass into the synovial fluid (SF).
We have recently demonstrated that patients affected with chronic inflammatory arthritides have higher apo A-I and TC SF levels, inversely correlated to local inflammatory indices such as white blood cell (WBC) count and IL-1ß, than do osteoarthritis (OA) patients [7].
Synovial lipoprotein concentrations appear to be correlated to their respective serum levels [8], but the interrelationship of synovial and serum values, their connection to synovial/systemic inflammation, and how individual lipids are affected have yet to be delineated.
The current work is an attempt to define in various arthritides the relationships between lipoproteins, inflammation severity, and synovial membrane permeability to single lipids, expressed as the ratio between synovial and serum concentrations. We have thus investigated SF and serum apo A-I, apo B, lipoprotein (Lp) (a), HDL-C, LDL-C, TG and TC levels in untreated RA, PsA, and OA patients.
Section snippets
Patients
Fourteen patients with RA, 14 with PsA, and 16 with OA attending the Outpatient Clinic of the Rheumatology Unit of the University of Padova Medical Center for diagnosis and/or treatment took part in this study. All the patients fulfilled the established diagnostic criteria for their respective diseases [9], [10], [11]. Patients with thyroid dysfunction, diabetes, renal disease, impaired hepatic function (aminotransferase levels > 2 × upper normal limits) or a history of alcohol abuse or smoking
Results
Patients' demographic and clinical characteristics as well as SF inflammatory indices are outlined in Table 1.
The age and disease duration in the OA, RA, and PsA groups were not significantly different. Serum CRP and SAA levels as well as SF WBC and PMN were significantly lower in the OA than in the RA and PsA patients (p < 0.05).
Discussion
Markedly different from those found in plasma, lipid levels are extremely low in normal human SF [13]. During inflammation, synovial permeability increases allowing proteins to enter the joint cavity. Depending on the degree of inflammation, protein SF/serum ratios increase reflecting diffusion of almost all proteins into the SF [14].
As far as larger molecules are concerned, both apo and lipoproteins seem to be able to flow through the synovial barrier and to enter into the SF cavity [8].
List of abbreviations
- RA
rheumatoid arthritis
- PsA
psoriatic arthritis
- OA
osteoarthritis
- HDL-C
high density lipoprotein-cholesterol
- LDL-C
low density lipoprotein-cholesterol
- TC
total cholesterol
- TG
triglycerides
- apo A-I
apolipoprotein A-I
- apo B
apolipoprotein B
- Lp(a)
lipoprotein (a)
- SF
synovial fluid
- WBC
white blood cell
- CRP
C-reactive protein
- SAA
serum amyloid A
- PMN
polymorphonuclear leukocytes
Acknowledgments
The authors are grateful to Mrs. Linda Inverso Moretti for editing the English version of this manuscript.
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