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ID PMID Title PublicationDate abstract
15258981 Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negati 2004 Sep The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.
15466896 Nutritional impairment in juvenile idiopathic arthritis. 2004 Dec OBJECTIVE: To investigate the relationship between nutritional impairment, measured by body mass index (BMI), expressed as an age- and sex-standardized standard deviation score (BMI SDS), and disease and patient characteristics in a UK cohort of children with juvenile idiopathic arthritis (JIA). A subgroup with available dietary information were analysed separately. METHODS: Important disease and patient characteristics (age, gender, disease subtype, swollen joint count, painful joint count, restricted joint count, treatment and dietary assessment) were assessed as potential explanatory measures of BMI SDS in a multiple linear regression. RESULTS: Data were collected on 123 consecutive patients. Twenty were nutritionally impaired. In multiple regression analysis excluding the dietary data, disease subtype [persistent oligoarthritis and polyarthritis (rheumatoid factor-negative)], five or more joints with reduced range of movement and being younger were associated with lower BMI SDS (P<0.001). When energy and protein intake were included in the analysis for a subgroup of children, the resulting model retained only disease subtype as a predictor of a low BMI SDS (P = 0.013). CONCLUSIONS: In this unselected population of children with JIA, 16% had evidence of undernutrition. The most commonly affected subtype was oligoarthritis, a previously unreported finding. There is no evidence from this study that this nutritional impairment results from inadequate food intake and it is likely that it is multifactorial in aetiology, disease subtype being the most important factor.
15338507 Deaths from arthritis and other rheumatic conditions, United States, 1979-1998. 2004 Sep OBJECTIVE: To analyze US trends in deaths from arthritis and other rheumatic conditions (AORC). METHODS: Multiple cause of death tapes from the National Center for Health Statistics from 1979 to 1998 were reviewed. Age, sex, and race-specific death rates were calculated. RESULTS: During 1979-1998, the annual number of AORC deaths rose from 5537 to 9367. In 1979, the crude death rate from AORC was 2.46 per 100,000 population; by 1998, it was 3.48. Rates age-standardized to the year 2000 population were 2.75 and 3.51, respectively. Annual crude and age-standardized death rates were higher among women than men and higher among blacks than whites and increased for all groups over the 20 years. Death rates were dramatically higher with increasing age. Three categories of AORC accounted for almost 80% of deaths: diffuse connective tissue diseases (34%), other specified rheumatic conditions (23%), and rheumatoid arthritis (22%). CONCLUSION: There are marked age, sex, and race-specific disparities in AORC death rates. AORC death rates may be underestimated because of (1) nonrecognition of inflammatory arthritis and (2) attribution of cause of death to conditions made more likely by arthritis, e.g., cardiovascular disease, or to complications from arthritis therapy. Further research into the causes of the disparities in death rates and the increase in death rates for men, women, blacks, and whites is necessary.
14524050 [Quality assurance of rheumatologic patient education]. 2003 Since 1989 patient education programmes for patients with rheumatoid arthritis, ankylosing spondylitis and other spondylarthropathies, systemic lupus erythematosus, vasculitis, fibromyalgia, and juvenile chronic arthritis and their parents have been developed by an interdisciplinary team of the German Society of Rheumatology (Deutsche Gesellschaft für Rheumatologie). Up to date, about 500 people were trained to be group leaders or specialised trainers with an associated train-the-trainer program. In 1999, the Society discharged preliminary guidelines for patient education in rheumatology. Prospective randomised studies demonstrated that patient education led both to an improvement of knowledge, self-efficacy and self-help activities and to an improvement of arthritis-related helplessness and pain, and a reduction of both temporary and permanent disability.
14716747 Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suff 2004 Jan The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). METHODS: A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. RESULTS: The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. CONCLUSIONS: Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered.
14614855 Beneficial autoimmunity to proinflammatory mediators restrains the consequences of self-de 2003 Nov Therapies that neutralize the function of TNF-alpha suppress rheumatoid arthritis (RA) but not osteoarthritis (OA). We show that patients suffering from RA but not OA have significant levels of autoantibodies directed to TNF-alpha. Thus, the immune system can selectively generate autoimmunity to proinflammatory mediators when such a response is beneficial for the host. A well-defined model of RA was used to elaborate the contribution of beneficial autoimmunity to the regulation of disease. We show that during the disease autoantibody production is elicited against few inflammatory, but not regulatory, mediators. Selective amplification of these beneficial antibodies by targeted DNA vaccines provided protective immunity. Epitope mapping revealed that anti-TNF-alpha immunity is highly restricted and excretes no crossreactivity to other known gene products. Its selective exclusion substantially exacerbated the disease. Administration of anti-TNF-alpha antibodies could then override this aggravation. This substantiates the significance of beneficial autoimmunity in restraining self-destructive immunity.
12810435 Inhibition of arthritis by systemic administration of endostatin in passive murine collage 2003 Jul OBJECTIVE: To investigate the arthritis inhibiting effect of endostatin, known to have potent antiangiogenic activity, systemically given to animal models of rheumatoid arthritis (RA). METHODS: Four kinds of monoclonal anti-type II collagen antibody followed by lipopolysaccharide (LPS) three days later were given to 6 week old, female Balb/c mice to induce arthritis. Three groups of mice received 0.2 mg/kg/day, 2 mg/kg/day, and 10 mg/kg/day of endostatin, respectively, whereas a control group received phosphate buffered saline (PBS). Endostatin or PBS was given for 13 days, starting before the development of arthritis. Arthritis was evaluated by arthritis scores and hind paw thicknesses. Mice were killed for histological examination on the 22nd day after the administration of monoclonal anti-type II collagen antibody. RESULTS: Arthritis developed within three days after LPS administration in both the control and endostatin treatment groups. No difference in the development rate of arthritis was noted between the control and endostatin treatment groups. Arthritis scores remained significantly lower in the endostatin 10 mg/kg/day group than in the control group. Hind paw thicknesses also remained significantly smaller in the endostatin 10 mg/kg/day group than in the control group. Histopathological examination showed that synovial thickening and subchondral bone erosion improved more in the endostatin treatment groups than in the control group. CONCLUSION: The systemic administration of endostatin had an arthritis inhibiting effect in RA animal models. Endostatin inhibited, in particular, pannus formation and bone destruction.
12673887 Efficacy of daily compared to intermittent administration of IL-1Ra for protection against 2003 Jan OBJECTIVE: To investigate the protective effect of interleukin-1 receptor antagonist (IL-1Ra) on bone and cartilage destruction in the induction phase of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA). METHODS: DBA/1J mice were immunized with type II collagen for induction of collagen-induced arthritis (CIA) and simultaneously given different intraperitoneal doses of IL-1Ra daily, thrice weekly or once a week. Clinical symptoms of arthritis were noted daily and assessed using a scoring system during the course of disease. Bone and cartilage destruction in the mice was assessed by radiographic and histological methods respectively. RESULTS: Mice injected with IL-1Ra daily were completely protected from the occurrence of arthritis after immunization with type II collagen. Moreover, these mice were also protected against bone and cartilage destruction. However, weekly or thrice weekly treatment with IL-1Ra had no effect on arthritis and bone and cartilage destruction. CONCLUSION: Daily administration of recombinant IL-1Ra, injected at the same time as arthritis induction, is effective in blocking the occurrence of inflammatory as well as destructive changes in CIA. Daily bolus injections of IL-1Ra may therefore be useful for protection against joint damage following minor joint injury, whereas the maintenance of appropriate blood levels of the antagonist may be critical for its therapeutic effect on chronic inflammatory arthritis.
12171568 Pyridinylimidazole based p38 MAP kinase inhibitors. 2002 Sep The p38 MAP kinase is thought to be involved in a variety of inflammatory and immunological disorders such as rheumatoid arthritis. The pyridinylimidazole class of compounds was the first to potently inhibit this kinase. Since the original reports of their efficacy, they have become the most widely studied series of inhibitors of this kinase. This framework has served as a starting point for further synthetic work and several compounds have entered clinical trials. These compounds have also been utilized to elucidate the role of p38 kinase in the immune system, and more recently have been used to examine the role of this kinase in central nervous system disorders.
14582328 [Polymorphism of human HLA-DRB1 leukocyte antigen alleles and its association to juvenile 2003 Sep Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were characterized at the molecular level in a group of Colombian children suffering juvenile rheumatoid arthritis (JRA). The distribution of these alleles was examined in a group of Colombian mestizo children (genetic admixture of Amerindians, Europeans and Africans) suffering from clinically distinct JRA subsets in order to detect HLA allele frequency differences in patients with different JRA subsets. A group of 65 patients with JRA and 65 controls were characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The oligotyping protocol recommended by the 12th International Histocompatibility Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was the allele most strongly associated with susceptibility to JRA (Fisher's p = 0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602 was also associated with susceptibility to a lesser degree (Fisher's p = 0.016, OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA-DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF = 0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical features was also compared. The presence of rheumatic factor was associated with the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p = 0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701 (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF = 0.97) was the one expressed most commonly. In the poliarticular group, the alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR = 8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p = 0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the MHC genes of mestizo children influence not only the clinical expression of the disease, but also the susceptibility to its development.
15228619 Treating psoriatic arthritis: how effective are TNF antagonists? 2004 Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy that commonly appears after the onset of the characteristic cutaneous lesions. This complication affects about 40% of patients with moderate to severe cutaneous disease. Analysis of synovial fluid and tissue in patients with PsA demonstrates a profile of high levels of tumor necrosis factor (TNF) plus other cytokines similar to those seen in patients with rheumatoid arthritis (RA). In the past, medical management of patients with this disease consisted of treatment with nonsteroidal anti-inflammatory agents. Patients with more severe disease have tried a number of different disease-modifying drugs including methotrexate, azathioprine, and gold salts. However, there is no evidence that these agents can arrest the progress of structural joint damage. Infliximab and etanercept are TNF antagonists that have demonstrated significant efficacy and safety in patients with RA. Clinical trials with these two agents in patients with PsA have shown significant improvement in the rheumatologic and cutaneous manifestations of the disease.
11920418 Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment wi 2002 Mar OBJECTIVE: To investigate the role of interleukin-17 (IL-17) in inflammatory arthritis by blockade with an IL-17 receptor/human IgG1 Fc fusion protein (muIL-17R:Fc) in adjuvant-induced arthritis (AIA) in the rat. METHODS: AIA was induced in 39 DA rats with the use of Freund's complete adjuvant. Rats received either 7.3 or 20 mg/kg of muIL-17R:Fc or phosphate buffered saline intraperitoneally every other day from the time of arthritis induction for approximately 17 days. Paw volume, arthritis severity, and weight were assessed every 3-4 days. Rats were killed between days 21 and 23 post-induction. Ankles were removed for quantitative radiology and histology and for immunohistochemistry for T cells. RESULTS: Treatment with muIL-17R:Fc attenuated paw volume in a dose-dependent manner. Both the 7.3 and 20 mg/kg doses of muIL-17R:Fc significantly reduced radiographic scores in the treated rats compared with the controls. The 20 mg/kg dose of muIL-17R:Fc significantly reduced histology scores compared with the controls. T cell numbers were unchanged in the muIL-17R:Fc-treated rats as a function of dose. CONCLUSION: In vivo blockade of IL-17 by muIL-17R:Fc treatment attenuated AIA and reduced joint damage, suggesting that IL-17 plays an important role in the inflammation and joint destruction of AIA. IL-17 may be a potential therapeutic target for inflammatory diseases in humans, such as rheumatoid arthritis.
12776157 Adenoviral delivery of IL-18 binding protein C ameliorates collagen-induced arthritis in m 2003 Jun Elevated concentrations of interleukin-18 (IL-18) are found in both serum and synovial fluid of patients suffering from rheumatoid arthritis (RA) and this cytokine has recently been implicated in the development of experimental arthritis. In this present study, we developed an IL-18 neutralizing intervention and examined its efficacy for local intra-articular treatment of experimental arthritis. To this end we constructed an adenoviral vector containing the murine IL-18 binding protein isoform c gene (AdCMVIL-18BPc). The constructed adenoviral vector was validated on replication deficiency, transfection efficacy and ability to express biological functional IL-18BPc. Intra-articular overexpression of IL-18BPc significantly reduced incidence of collagen-induced arthritis (CIA) in treated kneejoints. Affected kneejoints of IL-18BPc-treated mice showed less severe arthritis, characterized by reduction of inflammation and destruction of bone and cartilage. Local intra-articular IL-1BPc treatment in both knees provided additional protection against CIA incidence and severity in distal paws. Measurement of serum levels of specific collagen type (CII) Abs revealed a moderate reduction of circulating IgG2a anti-CII Abs, while IgG1 anti-CII Abs remained at similar level. The present study underlines the involvement of IL-18 as an important proinflammatory cytokine in onset of experimental arthritis. Furthermore, it shows that endogenous IL-18 can be blocked efficiently through local adenoviral overexpression of IL-18BPc, indicating that treatment with IL-18BPc might contribute to joint protection in RA.
11838858 Interferon-gamma:interleukin 4 ratios and associated type 1 cytokine expression in juvenil 2002 Feb OBJECTIVE: To compare synovial tissue cytokine mRNA expression between patients with juvenile rheumatoid arthritis (JRA) and a heterogeneous group of non-autoimmune arthropathies (controls) with respect to type 1/type 2 balance. METHODS: Thirty-five JRA (average 9.1 years' disease duration) and 13 control synovial tissues were studied. As a measure of the type 1/type 2 cytokine balance in a subset of the JRA and control tissues, interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) mRNA levels were measured by competitive fragment reverse transcription-polymerase chain reaction. To quantitate additional cytokines relevant to this balance, multiprobe ribonuclease protection assays were employed measuring IL-5, IL-10, IL-13, IL-15, IL-18, and IL-12 (p35 and p40 subunits). Immunohistochemistry was performed on JRA tissues using antibodies specific for IL-15 and IL-18. RESULTS: A higher IFN-gamma:IL-4 ratio (p = 0.034) was found in JRA tissues compared to controls. JRA tissues also displayed higher mRNA levels of IL-12p35 (p = 0.021), IL-15 (p = 0.002), and IL-18 (p = 0.017), but not IL-4 and IL-10. IFN-gamma expression in JRA, but not controls, correlated strongly with IL-12p35 (r = 0.63) and IL-12p40 (r = 0.73) levels. A subset of IL-15+ and IL-18+ cells was detected in JRA synovial tissues, largely within perivascular aggregates. CONCLUSION: JRA synovial tissue cytokine expression patterns indicate a type 1 bias, even in the later stages of disease. The strong correlation between IFN-gamma and IL-12 in JRA suggests a prominent role for IL-12 in promoting the type I bias, while IL-15 and IL-18 may also indirectly increase IFN-gamma expression and further bias the immune response.
15361396 Serum cytokine levels related to multiple dimensions of fatigue in patients with primary S 2004 Oct OBJECTIVE: To test whether serum levels of selected cytokines relate to different dimensions of fatigue in patients with primary Sjögren's syndrome (pSS). METHODS: Sixty female patients with pSS filled out a questionnaire to assess multiple dimensions of fatigue. Scores were compared with values in a population based control group (n = 139). Levels of interleukin (IL)1beta, IL2, IL6, IL10, and tumour necrosis factor alpha were measured in serum with commercial sandwich ELISAs. The relationship between self reported dimensions of fatigue and these serum cytokine levels was determined. RESULTS: Patients with pSS had high scores at all dimensions of fatigue (p<0.001): general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Fatigue levels were not related to serum cytokine levels. The incidental finding that reduced motivation was higher in patients with detectable serum levels of IL10 (p = 0.04) disappeared after correction for multiple testing. CONCLUSION: Fatigue is prominent in patients with pSS and involves all dimensions of fatigue. The findings do not suggest a widespread effect of circulating cytokines on multiple aspects of fatigue.
15308116 Expression of interferon-inducible T cell alpha chemoattractant (CXCL11) in the salivary g 2004 Sep To investigate the possible involvement of interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11) in the salivary gland lesions of Sjögren's syndrome (SS), I-TAC mRNA expression was assayed in cultured salivary epithelial cells by reverse transcriptase-polymerase chain reaction (RT-PCR). This transcript was not expressed by SS salivary epithelial cells in the absence of IFNgamma, but was expressed after cells were stimulated with IFNgamma. We found that IFNgamma was the only cytokine that induced I-TAC mRNA expression. I-TAC proteins were shown by ELISA to be secreted into the culture supernatants of SS salivary epithelial cells following IFNgamma stimulation. Moreover, immunohistochemical assays of minor salivary glands (MSG) showed that I-TAC was predominantly located in the ductal epithelium adjacent to lymphoid infiltrates in the SS salivary gland, indicating that ductal epithelial cells produce I-TAC proteins in response to stimulation with IFNgamma secreted by lymphocytes that infiltrate into SS salivary glands. In contrast, I-TAC proteins were virtually absent from normal salivary glands. These findings suggest that I-TAC is involved in the development of salivary gland lesions observed in SS.
15170932 Cartilage destruction in collagen induced arthritis assessed with a new biochemical marker 2004 Jun OBJECTIVE: To assess the ability of a marker of collagen type II degradation (CTX-II) to quantify cartilage turnover in vitro in cartilage explants and in vivo in rats with collagen induced arthritis (CIA). METHODS: Bovine articular cartilage explants were cultured in the presence of interleukin 1a, oncostatin M, and plasminogen to induce cartilage degradation. CTX-II, CTX-I (C-telopeptide fragment of collagen type I), glycosaminoglycan, and hydroxyproline contents in culture supernatants were measured. CIA was induced in 12-week-old female Lewis rats by immunization with bovine type II collagen. The incidence and severity of arthritis were monitored by measuring paw swelling, and urinary levels of CTX-II and CTX-I were determined. The knee joints of rats were histopathologically examined after sacrifice. Results. CTX-II but not CTX-I levels correlated well with collagen degradation in bovine articular cartilage in vitro quantified by hydroxyproline release. Urinary CTX-II levels as well as paw volume of CIA rats were significantly higher than normal rats on Days 21, 28, and 42 and were apparently correlated with cartilage destruction, assessed histopathologically. Urinary CTX-I level began to increase on Day 21, but only on Day 42 was it significantly different between CIA and normal rats. The elevation in CTX-I level appeared to occur later than that of CTX-II, in accord with the more delayed onset of bone erosion in the CIA model of rheumatoid arthritis. CONCLUSION: Urinary CTX-II may be a useful marker for evaluation of dynamics of cartilage destruction in CIA rats.
12718739 Etanercept in psoriatic arthritis. 2003 Feb Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, can lead to disability from progressive joint destruction and bony fusion. To date, conventional disease modifying antirheumatic drugs (DMARDS) have not convincingly lessened joint pain and inflammation in PsA and there is very little data on the limitation of radiographic progression with these agents. The biological agent etanercept (Enbrel, Amgen, Inc, Thousand Oaks, California, USA) is a soluble TNF receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis (RA). In a Phase II and Phase III trial, conducted in moderate-to-severe PsA, etanercept significantly reduced joint pain and swelling and lowered the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. A significant decline in structural damage was observed as early as 6 months after starting the drug. Etanercept also improved quality of life measures (Health Assesment Questionnaire [HAQ] and global assessment scores). Up to a third of patients experienced transient injection-site reactions. Rare cases of opportunistic infection, demyelinating disorders and aplastic anaemia have been reported, but a causal link has not been established. In summary, etanercept is a safe and effective agent for the treatment of PsA and represents a major advance in the therapy of this potentially crippling disease.
12576202 Immunomodulatory activity of the aqueous extract from rhizome of Smilax glabra in the late 2003 Mar Our previous paper has reported that the aqueous extract from Rhizoma Smilacis Glabrae (RSG) remarkably inhibited the primary inflammation of adjuvant arthritis (AA) in rats. In the present study, we further examined the activity of RSG and its mechanism on the secondary inflammation of AA. The administration of RSG (400 and 800 mg/kg) during the later phase significantly inhibited the swelling of the adjuvant-non-injected footpad of AA rats. The lipopolysaccharide-induced production of IL-1, TNF and NO by peritoneal macrophages was significantly reduced. In contrast, the extract significantly recovered the decrease in weight gain of the AA rats and Concanavalin A-induced T lymphocyte proliferation and IL-2 production by their splenocytes, while prednisolone (10mg/kg) showed a significant aggravation. Furthermore, RSG significantly recovered the picryl chloride-induced delayed-type hypersensitivity to almost normal levels from the higher or lower levels induced by different treatments of cyclophosphamide with a normalization of CD4/CD8 ratio. These results suggest that RSG exhibit an improvement on AA through down-regulating over-activated macrophages and up-regulating the dysfunctional T lymphocytes during the later phase of arthritis. Such characteristics of RSG on AA may be advantageous to the long-term treatment of clinical rheumatoid arthritis.
15593200 Segment-specific but pathologic laminin isoform profiles in human labial salivary glands o 2004 Dec OBJECTIVE: To assess the laminins in basement membrane of the labial salivary glands of patients with Sjogren's syndrome (SS) and healthy controls. METHODS: Labeling of laminin alpha1-alpha5, beta1, beta2, gamma1, and gamma2 chains was performed using immunohistochemistry with chain-specific monoclonal antibodies and pattern recognition analysis of the labeled specimens. RESULTS: Laminin alpha1, alpha2, and alpha4 chains were detected exclusively in the acinar basement membranes, whereas laminin alpha3, alpha5, beta1, gamma1, and gamma2 chains were also detected in ductal basement membranes. Laminin beta2 chain was not found. In patients with SS, laminin alpha1 and alpha2 chains were weakly labeled, but laminin alpha4 labeling was also intense in areas not infiltrated by lymphocytes. Pattern recognition analysis suggested that laminin alpha1, alpha2, and alpha4 chains were associated with acinar cells, myoepithelial cells, and tissue damage/repair, respectively. CONCLUSION: All salivary gland basement membranes signal through laminin 5, laminin 6, and laminin 10 trimers, but acinar basement membranes also signal through laminin 1, laminin 2, and laminin 8 trimers. Laminin alpha1 chain/laminin 1 may play a central role in the maintenance of acinar cells in healthy glands. This possibility was supported by the finding of variable expression of laminin alpha1 chain/laminin 1 in acinar basement membrane and its weak expression in SS with acinar cell atrophy. The impairment of myoepithelial laminin alpha2 chain/laminin 2 in patients with SS indicates a double defect in the acinar compartment and pathologic extracellular matrix-to-cell signaling, which may contribute to structural deterioration and functional abnormality of the exocrine glands.