Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3081298 | Therapeutic plasmapheresis and plasma exchange. | 1986 | Plasma exchange is a process in which large volumes of plasma, usually equivalent to one plasma volume, are exchanged with donor plasma or a plasma substitute. This permits the removal of antibody, immune complexes, inflammatory mediators, paraproteins, drugs, toxins, and other plasma constituents. Plasma exchange may also have an effect on the immune system by enhancing the function of the reticuloendothelial system, removing blocking antibody, increasing clearance of tumor cells, and making lymphocytes more vulnerable to immunosuppressive drugs. Over 100 diseases have been treated with plasma exchange with variable success. Results of controlled studies are less dramatic than those of earlier uncontrolled case reports. Reports of complications and even death have tempered initial enthusiasm. Now, over a decade since the initial promising reports began to appear in the literature, the role of plasma exchange remains undefined. | |
| 3532739 | Nonsteroidal anti-inflammatory agents: an update. | 1986 Oct | Nonsteroidal anti-inflammatory drugs (NSAIDs) provide potent analgesic, anti-inflammatory activity as a result of their inhibition of prostaglandin synthesis. They are highly bound to plasma proteins and have half-lives that vary from two hours to more than 24 hours. While gastrointestinal reactions are well known, the renal and hepatic toxicities of NSAIDs have only recently been characterized. Elderly patients in general may be at risk of toxicity and should be evaluated frequently. | |
| 3213266 | [Ulcer healing with ranitidine and antacids despite continued therapy with non-steroidal a | 1988 May | The aim of this study was to investigate the course of gastric and duodenal ulcers under ranitidin and antacid treatment during continuous NSAID therapy, and to answer the question of whether ulcers are an absolute contraindication for NSAID treatment. A total of 21 patients (17 females; four males; average age 58 years) with rheumatoid arthritis (18 patients), ankylosing spondylitis (two patients), and cervical spine syndrome (one patient) with gastric and/or duodenal ulcers, demonstrated by endoscopy, entered the study. Because of the severe course of the rheumatic disease present in every patient, there was a need to continue NSAID therapy. Gastric or duodenal ulcers were treated with 300 mg ranitidin and an aluminium-magnesium-hydroxide-containing antacid with an acid binding capacity of 280 mval/day. The course of healing of the ulcers was checked endoscopically and in part by biopsies (gastric ulcers). Within the period of 31 +/- 11 days, all duodenal ulcers under observation had healed. Of the gastric ulcers, 50% had healed completely while the others showed definite improvement. NSAID-induced ulcers were located in or close to the pylorus, contrary to the location of peptic ulcers. These data show that NSAIDs--if administration is absolutely necessary because of the severe course of the rheumatic disease--can be continued even in the presence of gastric or duodenal ulcers when administered with ranitidin and antacids. Because of hemorrhage and perforation in NSAID-induced ulcers, close clinical and endoscopic checks are necessary. Failures, even with the use of H2-blockers, have also been described. | |
| 2455485 | Binding of haptoglobin, inter-alpha-trypsin inhibitor, and alpha 1 proteinase inhibitor to | 1988 May | Synovial fluid from 201 normal and pathological knee joints was subjected to gel filtration by Sepharose CL-2B chromatography to separate hyaluronic acid (HA) from unbound proteins, which were retarded on this column. HA from all normal fluids was excluded from the gel and contained 1% or less bound protein. Synovial fluids taken from joints of patients with rheumatoid arthritis (RA) contained considerably more protein bound to HA. In 46% of RA samples the level of protein was greater than 4%, whereas only one fluid examined from osteoarthritic joints contained this amount. The proteins bound to HA from RA joints were identified by sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) and immunodiffusion techniques as the acute phase proteins alpha 1 proteinase inhibitor, inter-alpha-trypsin inhibitor, and haptoglobin. The average relative percentages of these proteins bound to HA were 17.6%, 32.6%, and 29.2% respectively. These HA-protein complexes could be generated in vitro by mixing normal (low protein) HA with any one of the three acute phase proteins. The HA-protein complexes formed in vitro with inter-alpha-trypsin inhibitor or haptoglobin, and those isolated from RA synovial fluids, were more resistant to degradation by oxygen derived free radicals (ODFR) than HA from normal fluids. From these findings we conclude that certain acute phase proteins diffusing into synovial fluid during inflammatory episodes may play an important part in protecting HA from depolymerisation by activated phagocytes. | |
| 3954279 | The erythrocyte sedimentation rate. Guidelines for rational use. | 1986 Apr | The erythrocyte sedimentation rate (ESR) is seldom the sole clue to disease in asymptomatic persons and is not a useful screening test. When the rate is increased, a careful history and physical examination will generally disclose the cause. An unexplained increase in the ESR is generally transitory and seldom due to serious disease. The test is most useful in diagnosing temporal arteritis and monitoring the patient's response to treatment. The test has little diagnostic value in rheumatoid arthritis but may be useful in monitoring disease activity when clinical findings are equivocal. The ESR is often normal in patients with cancer, infection, and connective tissue disease and is therefore of little use in excluding these diseases in patients with vague complaints. | |
| 3659248 | Adult-onset Still's disease; clinical and laboratory features, treatment and progress of 4 | 1986 Nov | The clinical and laboratory features, treatment, prognosis, complications and disability of 45 patients with adult-onset Still's disease were studied. Sixty per cent of the patients were female. Median age at onset was 25 years and median observation period after onset was 41 months. For 28 patients detailed data were available of the first month of illness. In only 43 per cent of these did the disease present with the classical triad of fever, arthritis and rash, although in the whole group eventually, fever with temperatures of 40 degrees C or more occurred in 84 per cent, arthritis in 98 per cent, and the typical rash in 82 per cent. In 32 per cent of the patients with rash, this was pruritic. Other features seen frequently were: lymphadenopathy (71 per cent), splenomegaly (36 per cent), pleuritis and/or pneumonitis (31 per cent), pericarditis (22 per cent), leucocytosis (98 per cent) and hepatic abnormalities (84 per cent). The high spiking fever was reduced to normal in six of 21 cases (29 per cent) by aspirin, in 19 of 27 cases (70 per cent) by indomethacin and in six of seven cases (86 per cent) by naproxen. In 16 of 21 cases (76 per cent) glucocorticoids reduced the systemic and/or joint symptoms. In three patients who remained febrile on glucocorticoids, indomethacin reduced temperature to normal. Eight patients whose joint disease improved on steroids later developed severe joint destructions. Thirteen patients received one or several slow-acting antirheumatic drugs. Only in eight of 18 trials (44 per cent) with one of these drugs did symptoms and signs improve. Fifty-one per cent of the 45 patients had self-limiting disease and 49 per cent had persistent disease with continuous activity for at least one year. At the time of evaluation 47 per cent of the 45 patients were in remission without medication, 33 per cent were in remission while on medication and 20 per cent had active disease. Three life-threatening complications occurred: two patients developed signs of cardiac tamponade and one almost died from diffuse intravascular coagulation. Disability was determined primarily by the course of the arthritis. At the time of review 43 per cent of the 45 patients had no joint destruction (Group 1), 24 per cent had destruction of at least one joint, but had no evidence of disease of the root joints (Group 2) and 33 per cent had destruction in at least one root joint (Group 3).(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1747946 | Transforming growth factor-beta 1 in rheumatoid synovial membrane and cartilage/pannus jun | 1991 Dec | Transforming growth factor (TGF)-beta has been shown to promote tissue repair and have immunosuppressive actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab')2 antibodies raised against recombinant human TGF-beta 1, we have detected TGF-beta 1 in the synovial tissue and cartilage/pannus junction (CPJ) from 18/18 patients with RA. TGF-beta 1 was found predominantly in the thickened synovial lining layer in RA, but also detected in a perivascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates. At the CPJ it was found both in cells at the distinct junction as well as in the transitional region of the diffuse fibroblastic zone. The cells staining for TGF-beta 1 were identified by double immunofluorescence staining as being from the monocyte/macrophage series as well as the type B synovial lining cells. TGF-beta 1 was also detected in the synovial membrane sections from 4/4 patients with systemic lupus erythematosus/mixed connective tissue disease and 5/8 patients with osteoarthritis, in a similar distribution to that seen in RA, and in the lining layer of 1/7 normal synovial membranes. These results add to histological evidence confirming that TGF-beta 1 is present in RA synovial cells and those from other arthritides. The distributions of TGF-beta 1 in RA synovial membrane reflects its known actions, as it can be detected at the CPJ, where it could induce repair, and close to activated cells upon which it may exert an immunosuppressive action. | |
| 3102596 | HLA DR, DQ, and DP antigen expression in rheumatoid synovial cells: a biochemical and quan | 1987 Mar 15 | Because an increased expression of HLA class II antigens appears to be a central feature in local lesions of rheumatoid arthritis (RA), we have developed specific tools to quantify Ia expression in RA at both the protein and mRNA levels. An original dot immunobinding assay and a quick blot hybridization with chain-specific HLA class II probes allowed quantification of HLA DR antigens and chain transcripts on small-size samples of adherent synovial lining cells (ASLC) from normal individuals or RA patients. These methods associated with Western blot techniques detecting class II and beta-chain expression showed that ASLC from RA patients freshly put in short-term culture expressed greater amounts of class II transcripts and proteins than ASLC from controls. Class II proteins and mRNA rapidly disappeared in culture. Recombinant interferon-gamma (rIFN-gamma) induced their re-expression. A study of the kinetics and levels of the HLA-D products showed similar patterns of activation in RA patients and controls. A qualitative analysis of HLA class II antigens synthesized in ASLC after rIFN-gamma induction was performed by two-dimensional gel electrophoresis. It revealed a normal pattern for alpha- and beta-chains in ASLC from normal and RA patients, thus eliminating the possibility that abnormal protein structure of Ia antigen expressed on ASLC is responsible for the activation of T cell immune responses in RA. Nevertheless, the invariant chain exhibited a particular pattern in ASLC with additional basic spots, and this might interfere with transport and glycosylation of HLA class II antigens in such cells. | |
| 1687401 | Benefits of oral contraception: thirty years' experience. | 1991 | A brief overview is presented of some benefits derived during 30 years of oral contraceptive use. Many benefits are significant improvements, and those women desiring to use oral contraceptives have benefited indirectly from lowered doses. Benefits include lowered incidence of endometrial and ovarian cancer, reduced cardiovascular risks, and a decreased incidence of rheumatoid arthritis. It is hoped that such an overview may prove useful during counseling of prospective users for whom oral contraceptives are recommended. | |
| 1836185 | Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific ant | 1991 Dec | Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains. | |
| 3282810 | B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lympho | 1988 Apr | The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3014141 | Intraarticular T lymphocytes in monoarticular and oligoarticular inflammatory joint diseas | 1986 Apr | T lymphocyte subpopulations and the expression of T cell activation antigens were determined in peripheral blood, synovial fluid and/or synovial tissues of patients with recurring monoarticular arthritis and patients with HLA-B27 associated oligoarthritis in comparison to patients with rheumatoid arthritis (RA). In individuals with monoarthritis or oligoarthritis, there was a normal T cell subset distribution, both in peripheral blood and in intraarticular sites, with only a small number of T cells bearing Ia antigens. This was in marked contrast to the patient group with RA that demonstrated a significantly decreased ratio of T helper/inducer to T suppressor/cytotoxic cells in addition to large numbers of Ia+ T cells in intraarticular sites. The expression of the Tac antigen was similar in all disease groups. | |
| 2211755 | The incidence of deep vein thrombosis after cementless and cemented knee replacement. | 1990 Sep | The incidence of deep vein thrombosis in 244 patients who had total knee replacement has been studied. In 120 the prosthesis was cemented and in 124 it was cementless. In all cases the replacement was primary and a porous-coated prosthesis with a porous-coated central tibial stem was used. Deep vein thrombosis was diagnosed by venography, and pulmonary embolism by perfusion scanning. The incidence of deep vein thrombosis in the cementless knees (23.8%) and in the cemented (25%) was approximately the same. The only significant predisposing factors for deep vein thrombosis in both groups were obesity, prolonged postoperative immobilisation, previous venous disease and hyperlipidaemia. | |
| 3489274 | The effects of synovial fluid macrophages and interleukin-1 on hyaluronic acid synthesis b | 1986 | The effects of peripheral blood monocyte and rheumatoid synovial fluid macrophage conditioned media were studied on hyaluronic acid (HA) metabolism of normal synovial fibroblasts. Both media stimulated HA synthesis about two-fold compared to controls (1% fetal calf serum). The activated mononuclear phagocyte conditioned media did not contain HA-degrading activity in these experiments. The effects of various concentrations of interleukin-1 (IL-1) on HA synthesis and proliferation of synovial fibroblasts were studied. Even at very low concentrations (0.1 IU IL-1/ml) HA synthesis was stimulated. With increasing concentrations HA synthesis did not increase but proliferation was stimulated. Stimulated fibroblasts synthesized mainly high molecular weight HA. Thus with IL-1-activation, normal synovial fibroblasts could not produce increased amounts of abnormal HA with decreased molecular weight. | |
| 3025094 | Altered function of synovial fluid granulocytes in patients with acute inflammatory arthri | 1986 Dec | In rheumatoid arthritis (RA) a chronic inflammatory state exists in which the synovial fluid is periodically filled with large numbers of polymorphonuclear leukocytes (PMNs). Oxygen radicals produced by these cells have been implicated as mediators of tissue damage and may be directly involved in the pathogenesis of RA. We examined the production of oxygen radicals by synovial fluid PMNs (SF-PMNs) and peripheral blood PMNs (PB-PMNs) by measuring chemiluminescence (CL) as well as superoxide anion (O2-) release. Increased spontaneous CL in the presence of luminol and increased CL in response to phorbol myristate acetate (PMA) was observed in SF-PMNs when compared to PB-PMNs. When zymosan was used as the stimulus in the absence of luminol, a slightly lower CL response was observed in SF-PMNs as compared to PB-PMNs. No significant differences were observed in the generation of O2- generation with any stimulus. Preincubation of normal PB-PMNs in 10% synovial fluid enhanced the luminol-dependent spontaneous and PMA-stimulated CL as well as zymosan-stimulated CL. When O2- release from normal PB-PMNs pretreated with 10% synovial fluid was compared to untreated controls, enhancement of spontaneous O2- release was observed. PMA- and zymosan-stimulated responses did not differ significantly from controls. Increased spontaneous and PMA-stimulated release of myeloperoxidase (MPO) was also observed in normal PB-PMNs pretreated with synovial fluid. These findings may explain the increased luminol-dependent CL since this type of CL requires the presence of MPO. Our findings suggest that the enhanced chemiluminescence observed in normal PMNs treated with synovial fluids may be related to increases in spontaneous O2- generation and myeloperoxidase release. Increased MPO release may account for enhanced CL observed in SF-PMNs. | |
| 1848487 | Lack of T cell oligoclonality in enzyme-digested synovial tissue and in synovial fluid in | 1991 Mar | The dominant presence of specific T-cell populations in the rheumatoid joint as detected by Southern blot analysis of T cell receptor (TCR) gene rearrangements would indicate local antigen recognition and T cell proliferation. We therefore studied TCR beta chain gene rearrangements using a C beta 2 probe in paired samples of T cell populations from synovial tissue and peripheral blood (n = 6) as well as synovial fluid (n = 16) and peripheral blood (n = 18) of patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells from healthy donors (n = 7) served as a control. T cells were studied directly after isolation or after non-specific expansion with OKT3 monoclonal antibody (MoAb) and T cell growth factor (TCGF). DNA samples were digested with EcoRI and HindIII to detect rearrangements to C beta 1 and C beta 2, respectively. Extra bands were detected in all EcoRI-digested DNA samples prepared from both freshly isolated and non-specifically expanded T cell populations of patients and healthy donors, possibly representing 'common' (V-) D-J rearrangements. Dominant rearrangements were found in only two out of 16 synovial fluid T cell populations (one freshly isolated and one expanded) and not in peripheral blood or synovial tissue derived T cell populations. No extra bands were detected in HindIII-digested DNA samples. To investigate the effect of in vitro culture techniques on rearrangement patterns we studied DNA samples prepared from synovial tissue T cells obtained both by outgrowth from tissue with TCGF or by enzyme digestion and subsequent expansion either with TCGF or with OKT3 MoAb and TCGF. Whereas the latter T cell population yielded 'common' rearrangements, the former T cell populations yielded different dominant rearrangements. These data indicate that oligoclonality of the T cell populations in synovial tissue and synovial fluid of patients with RA is a rare event. The data also show the influence of in vitro culture techniques on the result of TCR gene rearrangement analysis. | |
| 1707275 | Activation of CD16+ effector cells by rheumatoid factor complex. Role of natural killer ce | 1991 Apr | The role of natural killer (NK) cells in rheumatoid arthritis (RA) remains unclear. A pathogenetic function of rheumatoid factors (RF) also has not been defined. In the present studies, natural killer (NK) cells were examined as a model for FC gamma receptor type III-positive (FC gamma RIII+) cells, with regard to their interaction with RF. NK cell antigen CD16 (FC gamma RIII) and CD56 expression and functional NK and antibody-dependent cell-mediated cytotoxicity (ADCC) activity were compared in peripheral blood lymphocytes and autologous synovial fluid lymphocytes (SFL) of RA patients. Peripheral blood lymphocytes and SFL showed normal CD56 expression. In contrast, both the frequency and the density of CD16 antigen were decreased in SFL. Furthermore, diminished NK cytotoxicity and a significant decrease in ADCC were observed in SF NK cells. In subsequent in vitro studies with normal fresh NK cells, it was demonstrated that IgG-containing RF complexes from RA patients induced a modulation of FC gamma RIII structure from the NK cell surface, a decrease in NK activity, and a complete loss of ADCC. When purified RF was incubated with NK-enriched cell lines from RA patients, increased transcription and subsequent production of interferon-gamma and tumor necrosis factor alpha were observed. These data suggest a direct involvement of RF complexes in the pathogenetic process of chronic inflammation in RA. | |
| 3070731 | Idiotypic interactions between rheumatoid factors and other antibodies. | 1988 | An internal network of antibody idiotypes and anti-idiotypes has been considered important in controlling the production of antibodies reactive with exogenous antigens, and a current hypothesis proposes that some autoantibodies may be auto-anti-idiotypes. RF is often associated with bacterial (notably streptococcal) infections, as well as occurring in RA. Experimental animals immunised with streptococcal cell wall peptidoglycan-polysaccharide (PG-PS) complexes produce serum RF-like antibodies. In addition, repeated immunisation of mice with isolated IgM- or IgG-RF also produces an anti-PG-PS response, indicating that RF could act as an anti-idiotype to anti-PG-PS. Serum antibodies reactive with streptococcal PG-PS occur frequently in RA, and are notably of the IgG2 subclass. | |
| 3493780 | Inhibitor of interleukin-2 in rheumatoid synovial fluid. | 1987 Feb | Although large numbers of T cells infiltrate the synovium of patients with rheumatoid arthritis (RA), the responses of these cells, as present in the blood and synovial fluid (SF), to exogenous interleukin-2 (IL-2) and their production of IL-2 are diminished. To investigate this functional defect, RA SF were examined for the presence of inhibitors of IL-1 and IL-2. A factor was found which inhibited the IL-2-induced proliferation of mitogen-stimulated human T cells and the IL-1-induced proliferation of C3H/Hej mouse thymocytes, but not IL-1-induced fibroblast proliferation. On AcA 54 Ultrogel filtration, the inhibitory activity resided in a fraction with an apparent molecular weight of greater than 70 kd and a major pI of 6.8. The inhibitory effect of RA SF on lymphocyte proliferation was partially corrected with IL-2, but not with IL-1. In the presence of RA SF, normal lymphocytes showed not only a decreased response to exogenous IL-2, but also a decreased production of IL-2. The presence of an inhibitor of IL-2 in RA SF could contribute to the IL-2-related T cell defects observed in RA. | |
| 2845436 | The adenylate cyclase of rheumatoid synovial fluid macrophages is more sensitive for dl-5E | 1988 Aug | dl-5E, 19,14-di dehydro-carbo-prostacyclin (DDH-carbo PGI2), a stable prostacyclin (PGI2) derivative, but not prostaglandin (PG) E2, stimulated the adenylate cyclase of synovial fluid macrophages, isolated from rheumatoid patients with an active synovitis, in a dose dependent manner (10-1000 ng/ml). DDH-carbo PGI2 also stimulated synovial macrophage cAMP synthesis when injected into the knee joint. Exogenous arachidonic acid (AA) had little effect on cyclic-AMP (cAMP) formation or PGI2 release (assayed as 6ketoPGF1 alpha). It stimulated, however, the release of PGE2 and, to a lesser extent, thromboxane (Tx) A2 (measured as TxB2). |