Pro-inflammatory interleukins in the synovial fluid of rheumatoid arthritis associated with joint hypermobility.

BACKGROUND: Joint hypermobility (JH) is frequently seen in rheumatology; in some cases, such as rheumatoid arthritis (RA), it may represent a worsening of disease evolution. The aim of our study was to evaluate the influence of joint hypermobility on RA synovial fluid (SF) inflammation. Patients and methods. One hundred consecutive adult patients with RA and joint effusion of the knee were examined for the presence of JH. In the SF we evaluated volume, the number of white blood cells (WBC) and the levels of interleukin (IL)-1beta, IL-6 and IL-8 and prostaglandin E2 (PGE2). RESULTS: JH was associated with RA (JH-RA) in 18 patients, all of whom were female. Compared with non-JH RA, all the SF indices found in JH-RA were higher, although significant differences were observed only for volume, IL-8 and PGE2. CONCLUSION: In JH-RA, increased joint mobility seems to be associated with a more severe local inflammatory response, which may contribute to the more erosive evolution observed in our patients.

Bactericidal/permeability increasing protein and proinflammatory cytokines in synovial fluid of psoriatic arthritis.

OBJECTIVE: Bactericidal/permeability increasing protein (BPI) is a leukocyte product exerting antibacterial activity. Its production may be stimulated by cytokines, mainly Tumor Necrosis Factor (TNF) alpha. We studied BPI in the synovial fluid (SF) of psoriatic arthritis (PsA), a disease suspected to be influenced by infectious agents. METHODS: The levels of BPI and various indices of SF inflammation, including cytokines and its receptors, were determined in the SF of 18 patients with PsA and compared with those of 12 patients with rheumatoid arthritis (RA) and 9 with osteoarthritis (OA). RESULTS: The lowest SF levels of BPI were found in PsA (145.3 +/- 97.3 ng/ml), significantly lower than in RA (307.7 +/- 42.8 ng/ml, p = 0.0001) and similar to those in OA (151.1 +/- 52.4 ng/ml). Furthermore, only in PsA, and not in the RA and OA subgroups, correlations were observed between BPI and the indices considered, including TNF alpha (r = 0.746, p = 0.0004). CONCLUSION: Due to its relationship with local inflammation, SF BPI may play a role in the pathogenesis of arthropathies, in particular PsA.

Tryptophan catabolism in synovial fluid of various arthropathies and its relationship with inflammatory cytokines.

Synovial fluids (SF) from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), gout, and osteoarthritis (OA) were investigated for the levels of interleukin (IL)-1 beta, IL-6 and IL-8, tryptophan (Trp) and indoleamine 2,3-dioxygenase (IDO) activity. Significant differences exist in the levels of IL-1 beta between inflammatory arthritides RA, PsA and gout and non inflammatory arthritis, such as OA. The highest concentration of IL-1 beta was found in RA, that showed high levels also of IL-6 and IL-8. In the same disease we also found the highest IDO activity and the lowest Trp concentration. In addition, IDO activity seems to be related with the decrease in Trp, as demonstrated by the inverse correlation found between these two substances in the SF of all patients.

Clinical, laboratory and immunogenetic aspects of post-traumatic psoriatic arthritis: a study of 25 patients.

OBJECTIVE: In a previous study we demonstrated that the prevalence of trauma preceding arthritis was higher in patients with psoriatic arthritis (PsA) than in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS); of 300 consecutive patients with PsA, 25 (8%) had a history of trauma before (< 3 months) the onset of the disease. The present study was carried out to characterize the clinical, laboratory and immunogenetic profiles of post-traumatic (PT)-PsA. PATIENTS AND METHODS: The clinical and laboratory features of 25 patients with PT-PsA were studied at onset (first 6 months) and after a follow-up period of 1-7 years, and were compared with those of 275 PsA patients without any history of trauma (nonPT-PsA). HLA typing was performed in PT-PsA patients, and synovial fluid (SF) analysis, including interleukin (IL)-1 and IL-6 determinations, was carried out in 12 subjects with PT-PsA and in 32 with nonPT-PsA. RESULTS: No differences were observed between PT-PsA and nonPT-PsA patients with regard to their clinical evolution. ESR (p < 0.0001) and CRP (p = 0.005) were higher in PT-PsA than in nonPT-PsA patients at disease onset but not after follow-up. No differences were found in the other blood indices. SF analysis revealed higher IL-6 levels in PT-PsA than in nonPT-PsA patients (p < 0.0005). CONCLUSION: Our study demonstrates that the prevalence of trauma preceding arthritis is higher in PsA than in RA or AS. Clinical and laboratory findings in patients with PT-PsA differed from those with nonPT-PsA only at disease onset (first six months), however, showing an abrupt clinical presentation and a more acute phase response. This pattern may be related to the higher levels of IL-6 found in the SF of PT-PsA than in nonPT-PsA patients. However, during the follow-up period the two groups became indistinguishable, and no difference was observed between PT-PsA and nonPT-PsA regarding the evolution of the disease.

Clinical, laboratory and immunogenetic aspects of arthritis associated with chronic lymphocytic thyroiditis.

OBJECTIVE: Synovial fluid effusions and/or arthritis may be found in patients with chronic lymphocytic thyroiditis (CLT), even in the absence of hypothyroidism. Sometimes these arthropathies can be attributed to the rheumatic diseases frequently associated with CLT, but in some instances the arthritis seems to be independent of any of the diseases known to cause arthritis, and therefore remains unclassified. This study was carried out in an attempt to characterize the type and outcome of arthritis associated with CLT. METHODS: We performed a prospective study with a follow-up of 6.42 years (range 4-13) on 33 patients affected with CLT and presenting with arthritis. All conditions known to cause arthritis were previously excluded. Investigations included HLA typing, x-ray of the affected joints and, when possible, synovial fluid (SF) analysis with an interleukin (IL)-1 beta determination. Patients were divided based on their clinical presentation into two groups: those with polyarthritis and those with oligoarthritis. RESULTS: During the follow-up, 8 out of 16 patients with polyarthritis developed severe rheumatoid arthritis, characterized by bone erosions, high levels of SF IL-1 beta and an increased frequency of HLA DR4. The other 8 patients had polyarthritis in a mild, non-erosive form, which responded well to symptomatic drugs. Oligoarthritis, found in 17 patients, also showed a mild evolution, with frequent spontaneous remissions. The non-rheumatoid polyarthritis and oligoarthritis patients were characterised by the absence of bone erosions, low levels of SF IL-1 beta and an increased frequency of HLA DR3. CONCLUSIONS: We conclude that it is possible to find in association with CLT a type of inflammatory arthritis characterized by a mild, non-erosive evolution, low SF levels of IL-1 beta and an increased frequency of HLA-DR3. This arthritis seems to be independent of thyroid dysfunction and shows a clinical pattern similar to the arthritis usually found in connective tissue diseases.

Value of synovial fluid interleukin-1 beta determination in predicting the outcome of psoriatic monoarthritis.

OBJECTIVE: To investigate the value of synovial fluid analysis in predicting the outcome of psoriatic monoarthritis. METHODS: In synovial fluid from knee joints of 18 patients with psoriatic monoarthritis lasting less than six months, white blood cell count, acid phosphatase, lysozyme, and interleukin (IL)-1 beta were determined. ESR and serum C reactive protein were also measured. To define the outcome, the patients were monitored for at least three years and then subdivided into those with polyarthritis and those without. RESULTS: Among the blood and synovial fluid indices considered, synovial fluid IL-1 beta was the only variable which differed between the patients who developed polyarthritis, within three years and those without polyarthritis after this time, at 20.82(SD 8.79) v 4.19(4.73) pg ml-1, P < 0.0001). A correlation was found between synovial fluid IL-1 beta concentrations and the number of affected joints after three years (r = 0.739, P < 0.0001). CONCLUSIONS: Determination of synovial fluid IL-1 beta at disease onset may be useful in revealing the outcome of psoriatic monoarthritis since, among the variables considered in our study, this was the only one capable of predicting the evolution of monoarticular psoriatic arthritis to polyarthritis.

Synovial fluid levels of proinflammatory interleukins and their inter-relationships in elderly vs younger onset rheumatoid arthritis.

Elderly-onset rheumatoid arthritis (EORA) is thought to be different from younger-onset disease (YORA) for many reasons, including a more elevated acute phase response and a more abrupt onset; both events are mainly regulated by pro-inflammatory interleukins (ILs), in particular, IL-1, IL-6 and IL-8. To compare the synovial fluid (SF) levels of these ILs, and their relationship to local inflammation as well as the acute phase response, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) in the two RA subsets, we determined white blood cell (WBC) number, total protein (TP), IL-1beta, IL-6 and IL-8 concentrations in the SF of 50 patients, 15 with EORA and 35 with YORA. Both ESR and CRP were higher in EORA than in YORA. IL-6 was higher in SF of EORA (2111.37 +/- 1425.03 pg/mL) than YORA (1077.53 +/- 757.62 pg/mL, p = 0.002), while no difference was observed for SF IL-1beta and IL-8. There was a weak correlation between SF IL-6 and IL-1beta in EORA, whereas SF ILs and CRP and/or ESR did not show any correlation in both groups. Our study indicates that in EORA, as in other diseases occurring in the elderly, there are elevated levels of IL-6. Higher SF levels of IL-6 may be, at least in part, responsible for the different behavior of EORA with respect to YORA.

Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various arthropathies.

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1 beta, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL-beta detectable levels (> or = 20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA. IL-6 (mean +/- SD) (1610.37 +/- 1781.65 pg/ml) was higher in RA than in PA (672.47 +/- 867.40 pg/ml, p = 0.043) and OA (89.45 +/- 120.52 pg/ml, p = 0.0001). IL-8 (1042.72 +/- 698.64 pg/ml) was higher in RA than in PA (660.36 +/- 625.11 pg/ml, p = 0.03) and OA (89.9 +/- 45.88 pg/ml, p = 0.0001). A correlation between IL-1 beta, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration. Our findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.