Rheumatoid joint

Grootveld, M., Henderson, E.B., Farrell, A.J., Blake, D.R, Parkes, H.G. and Haycock, P. (1991). Oxidative damage to hyaluronate and gjucose in synovial fluid during exercise of the inflamed rheumatoid joint detection of abnormal low-molecular-mass metabolites by proton NMR spectroscopy. Biochem. J. 273, 459-467. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

This chapter addresses (1) the mechanisms, antioxidant defences and consequences in relation to free-radical production in the inflamed rheumatoid joint (2) lipid abnormalities in RA (3) the potential contribution of ox-LDL to RA (the role of ox-LDL in coronary heart disease is discussed in Chapters 2 and 3 and will not be fully discussed here) and (4) the therapeutic aspects of chain-breaking antioxidant interventions in RA. 

Mechanisms, Antioxidant Defences and Consequences of Free-radical Production in the Rheumatoid Joint... 

In collaboration with PA Baeuerle (Freibuig), active NF-xB has been detected immunohistochemically in rheumatoid synovium by using a polyclonal antibody directed against the Rel-A NLS subunit of NF-xB (M.L. Kus, unpublished observations). The antibody employed in these studies was considered to be activity specific because IxB sterically masks the NLS sequence. NF-xB activation by ROM in the rheumatoid joint may orchestrate some of the chronic inflammatory processes characteristic of this disease. It is plausible that lL-1 and TNFo generated in the inflamed synovium as well as the up-regulated expression of adhesion molecules may be under the influence of NF-xB. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Blake, 1989 Winyard et al., 1989). We suggest that within the inflamed rheumatoid joint (or the artery wall in atherogenesis), the production of ROM and proteases by endothelial cells and/or macrophages may cause the release of copper ions from Cp (see Section 2.2.3.2). It has been reported that Cp is cleaved faster in serum from patients with inflammatory diseases when compared to normal serum (Laurell, 1985). The oxidative modification of LDL by Cp-derived copper ions may explain the observation that increased serum cholesterol values are associated with accelerated atherosclerotic progression in men with high serum copper concentrations (Salonen et al., 1991). 

Blake, D.R., Blann( A., Bacon, P.A., Farr, M., Gutteridge, J.M.C. and Halliwell, B. (1983). Ferroxidase and ascorbate oxidase activities in synovial fluid from rheumatoid joints. Clin. Sci. 64, 551-553. 

Wang CR, Liu MF, Huang YH, Chen HC. Up-regulation of XCR1 expression in rheumatoid joints. Rheumatology (Oxford) 2004 43(5) 569-573. 

Koch AE, Volin MV, Woods JM, et al. Regulation of angiogenesis by the C-X-C chemokines interleukin-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheum 2001 44(1) 31 40. 

GM-CSF is undetectable in the serum of normal humans, and no normal cells have been shown to express this protein constitutively. Some transformed cells may constitutively express GM-CSF, and it is actively synthesised and secreted by antigen- and lectin-stimulated T cells and by endothelial cells and fibroblasts exposed to TNF, IL-1 or endotoxin. Other sources of GM-CSF include stimulated B lymphocytes, macrophages, mast cells and osteoblasts, whilst TNF and IL-1 can stimulate its production by acute myeloid leukaemia cells. Some solid tumours and synovial cells from rheumatoid joints may also express GM-CSF and this may be important in disease pathology. 

Figure 8.3. Morphological features of a normal and rheumatoid joint (a) the essential features of a healthy synovial joint (e.g. a knee joint) (b) the pathological features of a joint of a patient with rheumatoid arthritis.

The major neutrophil-activating factors within rheumatoid joints are immune complexes. These predominantly IgG-containing complexes vary considerably in size. Curiously, blood neutrophils do not generate reactive oxidants in response to soluble immune complexes, needing to be primed before they can be activated in this way (Fig. 8.4). It is therefore of interest to note that neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis have been primed in vivo and can secrete substantial quantities of reactive oxidants in response to these soluble complexes. Thus, it is extremely likely that these soluble immune complexes are responsible for activation of the secretion of reactive oxygen metabolites by infiltrating synovial-fluid neutrophils. This phenomenon may contribute to the events that lead to the destructive joint processes characteristic of this disease. 

Rosa chinensis Jacq. R. indica Lindl. Yue Je Hua (Tea rose) (leaf, fruit, flower bud) Essential oils.49 For arthritis, boils, cough, hematuria, rheumatoid joint pains, circulatory stimulant. 

Rosa chinensis Jacq. Essential oils.49 For arthritis, boils, cough, hematuria, rheumatoid joint pains, circulatory stimulant. 

Specific criteria for the diagnosis of rheumatoid arthritis in adults are listed in Table 16-1. In addition to the adult form of this disease, there is also a form of arthritis that occurs in children known commonly as juvenile rheumatoid arthritis, or by the more recent term juvenile idiopathic arthritis (JIA). Juvenile arthritis differs from the adult form of this disease—the age of onset (younger than 16 years) and other criteria help to differentiate these two types of rheumatoid joint disease.69,109 Drug treatment of adult and juvenile rheumatoid arthritis is fairly similar, however, with the exception that children may not respond as well to certain medications (e.g., hydroxychloroquine, gold compounds, penicillamine) compared to adults.79 80 Consequently, in this chapter most of the discussion of the management of rheumatoid arthritis is directed toward the adult form. 

Rheumatoid arthritis affects about 0.5 to 1.0 percent of the population worldwide.38,55 This disease occurs three times more often in women than in men, with women between the ages of 20 and 40 especially susceptible to the onset of rheumatoid joint disease.90 101 Rheumatoid arthritis often causes severe pain and suffering, frequently devastating the patient s family and social life as well as his or her job situation.5 55 The economic impact of this disease is also staggering medical costs and loss of productivity exceed 1 billion annually in the United States.5,55 Consequently, rheu-... 

Leflunomide (Arava) is a relative newcomer to the antirheumatic drug arsenal. This drug helps decrease pain and inflammation in rheumatoid joint disease, and leflunomide has been shown to slow the formation of bone erosions in arthritic joints.19 Leflunomide is also fairly well tolerated by most patients and may produce beneficial effects fairly soon (1 month) after beginning treatment.57,105 This drug is therefore a po-... 

Osteoarthritis far exceeds rheumatoid arthritis as the most common form of joint disease. The prevalence of osteoarthritis increases with age.2 Approximately 50 to 80 percent of people aged 65 years have osteoarthritis to some extent, and virtually everyone over 75 years has some degree of osteoarthritic joint disease.14 In contrast to rheumatoid joint disease, osteoarthritis does not seem to be caused by an immune response,... 

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