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ID PMID Title PublicationDate abstract
11218726 [Cytokine balance in the pathogenesis of rheumatoid arthritis]. 2001 Feb Rheumatoid arthritis (RA) is a common, frequently severe, chronic inflammatory disease. Although the cause of RA remains unknown, recent advances in understanding its pathogenesis have been substantial. Despite the use of a variety of medications, the treatment of RA is not fully effective in most patients. A T-helper type 1 (Th1)/T-helper type 2 (Th2) cytokine imbalance has been suggested to be of pathogenic importance in several diseases. In this review, the information of cytokine balance in both the experimental model of arthritis and patients with arthritis were summarized. Furthermore, to characterize the cytokine balance at a single cell level, we analyzed the subtypes of cytokine-secreting cells in an experimental model of arthritis using a dual color enzyme-linked immunospot assay (Stardust assay) which we newly developed. These information including our findings might provide us the clue for diagnosis and therapy of arthritis.
10378709 CD5 and CD23 expression on B cells in peripheral blood and synovial fluid of rheumatoid ar 1999 Apr METHODS: We have studied in peripheral blood (PB) and synovial fluid (SF) of 31 patients diagnosed with rheumatoid arthritis (RA), the expression of CD5 and CD23 antigens on B cells, and the levels of soluble CD23 (sCD23), interleukin-4 (IL-4) and tumour necrosis factor alpha (TNF-alpha). We have also correlated the results with the disease activity index. RESULTS: CD5+ B cells are expanded in SF and, moreover, show higher expression of CD23 than CD5 - B cells. Twelve patients had detectable levels of IL-4 in plasma and 10 in SF (nine patients in both samples); the absence of IL-4 was related to a higher expression of CD23 on CD5 + B cells and with higher levels of sCD23. A negative correlation was found in SF between TNF-alpha and sCD23 levels. CONCLUSION: There is no correlation between disease activity index and the different parameters studied (expression of CD5 and CD23 on B cells, sCD23, IL-4 and TNF-alpha levels) either in plasma/PB or in SF.
10323453 p205 is a major target of autoreactive T cells in rheumatoid arthritis. 1999 May OBJECTIVE: The p205 autoantigen and interleukin-2 (IL-2) function synergistically to stimulate T lymphocytes from patients with rheumatoid arthritis (RA), and a p205-derived amino acid sequence is identical to an immunoglobulin sequence located within a domain that is reactive with rheumatoid factors (RF). This study was conducted to analyze in detail the T cell immune response against p205 and to investigate whether immunity to p205 may play a role in T cell-mediated immunopathology in active RA. METHODS: Cibachron blue, protein A-Sepharose, and gel filtration on Sephacryl were used successively to enrich p205 from synovial fluid (SF). T lymphocytes from RA patients were isolated from the peripheral blood (PB), lymph nodes, and SF, and p205 and peptides derived from known sequences were assessed by T cell proliferation assays in the presence of IL-2. RESULTS: P205-specific proliferation of T cells was observed in PB as well as in SF. When p205 was isolated from RA SF, proliferation of RA T cells peaked on day 3. With p205 purified from SF from trauma patients, there was a significant shift of the maximum T cell proliferation to day 8. T cells were of CD4 or CD8 phenotype, and B cells did not proliferate to a significant degree. The T cell response to p205 was always higher for SF mononuclear cells (SFMC) compared with PBMC (P < 0.001). In 1 RA patient who underwent repeated leukapheresis, this led to a reproducible decline in p205-specific T cell proliferation to control levels. PB T cells specifically proliferating in response to p205 were detected in 20 of 32 RA patients (63%). Of 26 patients with other inflammatory rheumatic diseases, only 1 showed a minor response to p205, while normal donors did not demonstrate a significant T cell proliferation. A synthetic p205-derived peptide, with an amino acid sequence identical to an immunoglobulin sequence located in the area where RF binds, was reactive with T cells from RA patients. CONCLUSION: P205 appears to be a major target of autoreactive T cells in RA. P205-specific T cells are primed and more abundant at the site of inflammation. As a T cell target in RA, p205 may well be an antigen involved in the initiation of RF production.
9531325 Extracellular granzymes A and B in humans: detection of native species during CTL response 1998 Apr 1 Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including that termed granule exocytosis. The latter pathway consists of vectorial secretion of perforin and a family of granule-associated serine proteases (granzymes) to the target cell. To establish whether granzymes are released extracellularly during cytolytic reactions in vivo, ELISAs that measure the native enzymes were developed and were found to specifically detect granzyme A (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (median)), whereas significantly higher levels were present in patients with ongoing CTL response, i.e., patients suffering from infections by EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of patients with active rheumatoid arthritis. The measurement of soluble granzymes should be useful to assess clinical disorders associated with activated CTL and NK cells. Furthermore, these results suggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death.
9690723 Peptic ulcer therapy with cimetidine versus tripotassium dicitrato bismuthate in rheumatoi 1998 Apr AIM: To compare the efficacy of cimetidine and tripotassium dicitrato bismuthate (TDB) in arthritic patients who had developed gastric (GU) or duodenal (DU) ulceration while taking non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Eighty-six rheumatoid arthritis (RA) patients affected by endoscopically proven DU (n = 44) or GU (n = 42), and on chronic NSAID therapy which was not suspended during anti-ulcer therapy, were randomized to cimetidine (400 mg t.d.s.) or TDB (120 mg q.d.s.). A repeat endoscopy was planned after 4 weeks (and 8 weeks, in case of failed healing). The patients who were unhealed after 8 weeks of therapy were allocated to the alternative anti-ulcer drug for a further 8 weeks without interrupting the anti-inflammatory therapy. RESULTS: At week 4 of therapy. 14/24 (58%) DU and 9/20 (45%) GU patients treated with cimetidine were healed, compared with 12/20 (60%) and 10/22 (45%) TDB-treated patients (N.S.). At week 8 of therapy, the DU healing rates were 15/24 (63%) with cimetidine and 14/20 (70%) for TDB. The corresponding GU healing rates were 12/20 (60%) with cimetidine and 13/22 (60%) for TDB (N.S.). At week 16, complete healing with cimetidine was observed in 67% of DU and 57% of GU patients unhealed with TDB; the corresponding figures in the patients crossed to TDB were 83% for DU and 63% for GU patients (N.S. vs. cimetidine). CONCLUSIONS: No statistically significant difference was found between the healing activities of cimetidine and TDB in rheumatoid arthritis patients with peptic ulcer who did not interrupt their NSAID treatment for arthritis. This trial showed that the continued consumption of NSAIDs appears to slow the ulcer healing process, especially in GU patients.
11727846 Changes in plasma homocysteine in arthritis patients starting treatment with low-dose meth 2001 In 15 patients with rheumatoid arthritis (RA) (n = 13) or psoriatic arthritis (PsA) (n = 2) p-homocystcine and erythrocyte folate (erc-FA) were measured before start of methotrexate (MTX) treatment, after 4 weeks of MTX treatment (median 10 mg per week), and after further 4 weeks of treatment with MTX (median 12.5 mg per week) supplemented with folic acid (FA) (15 mg per week). Mean p-homocysteine were 12.3 +/- 3.4 micromol/l, 14.6+/-5.8 micromol/l (p<0.05) and 10.3+/-3.0 micromol/l (p<0.01) respectively. P-homocysteine concentrations were negative correlated to erc-FA after 4 weeks (rho -0.58; p<0.05). It is concluded that treatment with MTX induces a significant rise in p-homocysteine that is neutralised by FA supplementation. Supplementation with FA from the start of MTX treatment is recommended considering the increased risk of cardiovascular disease that is associated with elevated concentrations of p-homocysteine.
9486004 Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patien 1997 Jul OBJECTIVE: To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). METHODS: Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay. RESULTS: The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS. CONCLUSION: There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.
9872478 Internuclear ophthalmoplegia in systemic lupus erythematosus. 1998 Dec OBJECTIVES: To describe and review internuclear ophthalmoplegia (INO) in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A population of 268 SLE patients was retrospectively studied. INO was clinically defined as palsy of the ipsilateral rectus muscle and failure in contralateral eye adduction with dissociated nystagmus. A systematic review of the literature was made using MEDLINE (Silver-Platter) between 1966 and 1997, and for completeness, earlier references cited in identified articles. RESULTS: Four women with INO were identified. Their mean age at INO diagnosis was 38 years, and mean delay from diagnosis of SLE to INO was 6 years. INO was unilateral in all and coincided with disease activity in three. Cardiovascular risk factors were present in three. Magnetic brain resonance showed multiple and hyperintense (T2) lesions in white matter without correlation with clinical features. Other ancillary tests were not helpful for diagnosis. Corticosteroid therapy resulted in full resolution of INO in three cases. Review of 14 additional cases from the literature showed a similar experience. CONCLUSIONS: INO is uncommon in SLE, but it should be suspected in young patients with active disease and impairment of ocular movements. Diagnosis relies largely on clinical grounds. Neuroimaging is of little help. Steroid therapy seems effective in improving eye movements.
9502767 Interleukin 15 is produced by endothelial cells and increases the transendothelial migrati 1998 Mar 15 The capacity of endothelial cells (EC) to produce IL-15 and the capacity of IL-15 to influence transendothelial migration of T cells was examined. Human umbilical vein endothelial cells expressed both IL-15 mRNA and protein. Moreover, endothelial-derived IL-15 enhanced transendothelial migration of T cells as evidenced by the inhibition of this process by blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial migration of T cells by activating the binding capacity of the integrin adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility. In addition, IL-15 induced expression of the early activation molecule CD69. The importance of IL-15 in regulating migration of T cells in vivo was documented by its capacity to enhance accumulation of adoptively transferred human T cells in rheumatoid arthritis synovial tissue engrafted into immune deficient SCID mice. These results demonstrate that EC produce IL-15 and imply that endothelial IL-15 plays a critical role in stimulation of T cells to extravasate into inflammatory tissue.
9259421 Development of in vitro model systems for destructive joint diseases: novel strategies for 1997 Aug OBJECTIVE: To establish a novel 3-dimensional (3-D) in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA). METHODS: Two distinct culture systems were developed, consisting of RA synovial membrane and articular cartilage explants or interactive RA synovial cell/chondrocyte cultures embedded in 3-D fibrin matrices. The expression of proteolytic enzymes, chondrocyte matrix architecture, and matrix degradation parameters was analyzed by immunohistochemistry. RESULTS: Of 28 RA explant cultures, 16 displayed an invasion of synovial tissue into the cartilage explants, compared with 1 of 8 osteoarthritis explants. The expression of collagenase and vascular cell adhesion molecule 1 could be demonstrated at the cartilage-pannus junction. Of 20 interactive cell cultures, 18 revealed invasive behavior and remained vital for extended periods of time. CONCLUSION: The models presented allow us to study distinct aspects of destructive joint diseases under in vitro conditions that resemble human pathology. Moreover, our model is able to supplement animal experiments in basic research and drug testing.
9572059 New horizons for therapy based on the boron neutron capture reaction. 1998 Apr Boron neutron capture therapy (BNCT) is currently undergoing clinical trials in the USA, Japan and The Netherlands with patients afflicted with deadly brain cancer (glioblastoma multiforme) or melanoma. This therapy relies on a binary process in which the capture of a slow neutron by a 10B nucleus leads to an energetic nuclear fission reaction, with the formation of 7Li3+ and 4He2+ and accompanied by about 2.4 MeV of energy. The fleeting 7Li3+ and 4He2+ travel a distance of only about the diameter of one cell, and they are deadly to any cell in which they have been produced. Research in progress is concerned with the development of advanced boron agents and neutron sources, other than nuclear reactors, for the treatment of a variety of cancer types using novel 10B delivery methods. Non-malignant diseases such as rheumatoid arthritis offer additional opportunities for BNCT. The entire BNCT area awaits commercialization.
9546466 Is there a future for hinged prostheses in primary total knee arthroplasty? A 20-year surv 1998 Mar The Blauth prosthesis is a hinged total knee replacement. We have evaluated 422 consecutive primary total knee arthroplasties using this design in 330 patients with a maximum follow-up of 20 years (mean 6). The mean age of the patients at the time of operation was 70 years (29 to 87). Using endpoints of infection, removal because of aseptic loosening, removal for any cause, and the worst case as definitions of failure, the cumulative rates of survival at 20 years were 93.6%, 96.0%, 94.4% and 86.8%, respectively. The cumulative rate of survival of the patients themselves was 14.4% (24% in patients with osteoarthritis and 9% in these with rheumatoid arthritis) after 20 years. Our survivorship analysis shows that hinged knee prostheses, when they are biomechanically well designed, can yield a satisfactory long-term outcome, similar to those of the best prostheses of the resurfacing type. Hinged knee prostheses continue to be of value in patients with severe deformity or instability of the knee.
11169216 Cytokine production in arthritis susceptible and resistant rats: a study with arthritogeni 2001 Feb The basis of the different susceptibility to bacterial cell wall-induced arthritis between Lewis and Fischer rats is unclear. Likewise, it is not known why cell walls of some species of Lactobacillus are arthritogenic and those of others are not. With these two questions in mind, we investigated the role of anti-inflammatory (interleukin (IL)-10, IL-4) and proinflammatory (tumour necrosis factor (TNF)-alpha, IL-1 beta) cytokines in Lewis and Fischer rats injected intraperitoneally with cell walls from arthritogenic or nonarthritogenic species of Lactobacillus. Cytokine levels in the serum and in vitro production by peritoneal macrophages and splenocytes were studied. The results obtained indicate that the differences in the production of IL-10, IL-4, TNF-alpha or IL-1 beta do not explain the difference in the arthritis susceptibility between Lewis and Fischer rats. Likewise, the arthritogenicity of different Lactobacillus cell walls appears not to be dependent on their capacity to stimulate cytokine production.
9324019 Deficient Fas ligand expression by synovial lymphocytes from patients with rheumatoid arth 1997 Sep OBJECTIVE: To examine the expression and function of CD95 (Fas) and its ligand in rheumatoid arthritis (RA). METHODS: We used flow cytometry and reverse transcriptase-polymerase chain reaction methods to assess lymphocyte expression of CD95 and its ligand. We also examined whether lymphocytes could undergo Fas-mediated apoptosis with anti-CD95 monoclonal antibody (MAb) or human Fas ligand-expressing fibroblasts, and if synovial fluid contained a soluble factor(s) that could inhibit such interactions. Finally, we determined whether anti-CD3 MAb could induce synovial T cells to express the Fas ligand in vitro. RESULTS: Nearly all RA synovial fluid or synovial tissue lymphocytes expressed CD95 and could be induced to undergo apoptosis by CD95 crosslinking. We did not detect a soluble inhibitor in RA synovial fluid that could account for the survival of CD95+ synovial cells in vivo. Instead, we detected little or no expression of Fas ligand by RA synovial lymphocytes. However, we could induce such cells to express Fas ligand with anti-CD3 MAb or phorbol ester and ionomycin in vitro. CONCLUSION: There is ineffective clearance of activated cells in the RA joint due to deficient expression of the Fas ligand.
9485208 A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by a 1998 Jan CD137 (ILA/4-1BB) is a member of the tumor necrosis factor receptor family and regulates activation, proliferation and programmed cell death in T lymphocytes. Here we show the existence of a soluble form of CD137 (sCD137) of 16 kDa. sCD137 is released by activated lymphocytes, and in contrast to membrane-bound CD137, expression of sCD137 seems to be restricted to lymphocytes. sCD137 is generated by alternative splicing and two splice variants were identified. sCD137 is present at low levels in sera of some healthy donors (5/12; mean = 0.18 ng/ml) and is significantly enhanced in sera of patients with rheumatoid arthritis (12/12; mean = 3.58 ng/ml).
10693884 The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody sp 2000 Feb OBJECTIVE: To compare and investigate antihistone and antichromatin antibody responses as well as clinical variables in patients with systemic lupus erythematosus (SLE) who were either positive (LEC+) or negative (LEC-) for the lupus erythematosus (LE) cell phenomenon. METHODS: The binding properties of LEC+ and LEC- SLE sera to chromatin-associated nuclear antigens (histones H1, H2A, H2B, H3, H4; complexes of H2A-H2B, [H2A-H2B]-DNA, H1-DNA; total and H1-stripped chromatin; native and denatured DNA) were investigated. In addition, sera from patients with drug-induced lupus (by procainamide, hydralazine, or quinidine), as well as from patients with rheumatoid arthritis and osteoarthritis, were assessed. Enzyme-linked immunosorbent assay was used to detect specific antibody binding. RESULTS: Mirroring the important role of histone H1 in the formation of LE cells, anti-histone H1 reactivity was 8-fold higher in LEC+ sera than in LEC- sera. In addition, reactivities to most of the other antigens tested, i.e., other histones and histone-DNA complexes as well as chromatin and DNA, were significantly higher in LEC+ sera than in LEC- sera. All but 1 serum sample from the patients with drug-induced lupus were negative for LE cell formation as well as for anti-histone H1 reactivity, but displayed high antibody reactivities to histone-DNA complexes, including chromatin. Sera from patients with rheumatoid arthritis and osteoarthritis did not show significant binding to these antigens. When comparing the clinical features of LEC+ and LEC- SLE patients, severe organ involvement, including nephritis and central nervous system involvement, was common in the LEC+ group, but rare in the LEC- group. CONCLUSION: A positive LE cell phenomenon not only correlated with the presence of high anti-histone H1 antibody levels in SLE, but also indicated serologically and clinically active disease with major organ involvement.
9558730 Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids. 1998 The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumour necrosis factors, occurs rapidly following trauma or invasion of the body by pathogenic organisms. The cytokines mediate the wide range of symptoms associated with trauma and infection, such as fever, anorexia, tissue wasting, acute phase protein production and immunomodulation. In part, the symptoms result from a co-ordinated response, in which the immune system is activated and nutrients released, from endogenous sources, to provide substrate for the immune system. Although the cytokine mediated response is an essential part of the response to trauma and infection, excessive production of pro-inflammatory cytokines, or production of cytokines in the wrong biological context, are associated with mortality and pathology in a wide range of diseases, such as malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant cytokine receptor antagonists and nutrients. Among the nutrients, fats have a large potential for modulating cytokine biology. A number of trials have demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3 polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate that a range of fats can modulate pro-inflammatory cytokine production and actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1 production and tissue responsiveness to cytokines, fats rich in n-3 polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids decrease tissue responsiveness to cytokines and IL6 production is enhanced by total unsaturated fatty acid intake. There are a large number of potential cellular mechanisms which may mediate the effects observed. The majority relate to the ability of fats to alter the composition of membrane phospholipids. As a consequence of alterations in phospholipid composition, membrane fluidity may change, altering binding of cytokines to receptors and G protein activity. The nature of substrate for various signalling pathways associated with cytokine production and actions may also be changed. Consequently, alterations in eicosanoid production and activation of protein kinase C may occur. We have examined a number of these potential mechanisms in peritoneal macrophages of rats fed fats with a wide range of fatty acid composition. We have found that the total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal macrophages relates in a positive curvilinear fashion with dietary linoleic acid intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear fashion to linoleic acid intake; that leukotriene B4 production relates positively with dietary linoleic acid intake over a range of moderate intakes and is suppressed at high intakes, while PGE2 production is enhanced. There was no clear relationship between linoleic acid intake and membrane fluidity, however fluidity was influenced in a complex manner by the type of fat in the diet, the period over which the fat was fed and the presence of absence of TNF stimulation. None of the proposed mechanisms, acting alone, can explain the positive effect of dietary linoleic acid intake on pro-inflammatory cytokine production. However each may be involved, in part, in the modulatory effects observed.
11712687 The pathogenesis of autoimmune diseases. 2001 Autoimmunopathies are chronic inflammatory diseases which can be subdivided into several specificities on the ground of the clinical picture as well as serological findings and involvement of organ systems like the kidney, central nervous system or the hematopoietic system. The pathogenesis of these diseases is incompletely understood. With the exception of rare diseases in which the autoantigens are known, in the most frequent autoimmunopathies like rheumatoid arthritis or Systemic Lupus Erythematosus (SLE) only some partial aspects of the pathogenetic scenario are understood and rather well substantiated by experimental data. In RA, there are controversies concerning the central involvement of T-lymphocytes and/or synovial fibroblasts in the initiation of the diseases. It is meanwhile well known that TNF-alpha and possibly other related cytokines are involved at least in the perpetuation of the inflammatory cascades. Specific blockade of TNF-alpha leads to rapid improvement of RA disease activity and can prevent tissue destruction. An intriguing hypothesis postulates a central role for a dysregulated apoptosis in the development of SLE. In this review we will concentrate on pathogenetic concepts of autoimmune diseases as exemplified by RA and SLE.
10967025 Presence of the 55 kDa glycosylation inhibiting factor in human serum. 2000 Sep An ELISA system for the human glycosylation inhibiting factor (GIF) was established using polyclonal antibodies against highly purified 13 kDa recombinant human GIF, and the concentration of GIF in the sera of healthy donors and patients with various diseases was determined. GIF was detected in the sera of most healthy individuals and its concentration tended to increase with age. It was also found that the serum GIF levels markedly increased in some patients with rheumatoid arthritis or malignant tumors. Analysis of serum samples by SDS-PAGE and immunoblotting revealed a 55 kDa protein that has both the GIF antigenic determinant and the TCR alpha chain determinant. A 13 kDa GIF was not detected in the sera. In view of our previous findings on antigen-specific GIF from murine suppressor T cell hybridomas indicating that the 55 kDa GIF is a post-translationally formed conjugate of a TCR alpha chain with 13 kDa GIF, we suspect that the 55 kDa GIF detected in human sera is a human homologue of the murine 55 kDa GIF.
9739500 Epidemiology and optimal management of polymyalgia rheumatica. 1998 Aug Polymyalgia rheumatica (PMR) is a disease of unknown aetiology that occurs in elderly patients, predominantly affecting the Caucasian population. The disease has a slightly higher prevalence in women than in men. There is ongoing discussion regarding the relationship between PMR and giant cell arteritis; an increasing number of studies indicate that they are closely related. PMR has also been linked with rheumatoid arthritis, myopathy and malignant disease. Oral corticosteroids remain the mainstay of drug therapy for PMR. These drugs usually induce prompt relief of symptoms, and some authors consider this dramatic response to be diagnostic for PMR. However, the ideal initial dosage, the duration of treatment and the optimal tapering schedule are much debated. Other drugs, such as methotrexate and azathioprine, have been suggested as corticosteroid sparing agents. Nonsteroidal anti-inflammatory drugs are generally considered to be unsuitable for the long term treatment of PMR.