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ID PMID Title PublicationDate abstract
22194660 Beyond fat mass: exploring the role of adipokines in rheumatic diseases. 2011 The cloning of leptin in 1994 by Zhang et al. introduced a novel concept about white adipose tissue (WAT) as a very dynamic organ that releases a plethora of immune and inflammatory mediators, such as adipokines and cytokines, which are involved in multiple diseases. Actually, adipokines exert potent modulatory actions on target tissues involved in rheumatic diseases including cartilage, synovial, bone and immune cells. The goal of this paper is to elucidate the recent findings concerning the involvement of adipokines in rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and systemic lupus erythematosus (SLE).
21377916 IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. 2011 Apr IL-6 activates various cell types carrying the membrane bound IL-6R (classical IL-6 signaling) as well as IL-6R(-) gp130(+) cells via the soluble IL-6R (IL-6 trans-signaling). IL-6 signaling plays a pivotal role in controlling the differentiation and activation of T lymphocytes by inducing the Jak/STAT-3 and the Ras/Erk/C/EBP pathways. In particular, IL-6 modulates the resistance of T cells against apoptosis, induces activation of T helper cells and controls the balance between regulatory T cells and Th17 cells. Importantly, recent findings suggest that blockade of IL-6 signaling is effective in treating experimental models of autoimmune and chronic inflammatory diseases such as inflammatory bowel diseases, diabetes, multiple sclerosis, asthma and rheumatoid arthritis as well as models of inflammation-associated cancer. Thus, anti-IL-6/anti-IL-6R strategies emerge as promising novel approaches for therapy of inflammatory diseases in humans. In this review article, we discuss the latest findings on the role of IL-6 in experimental models of autoimmunity and cancer, as well as clinical perspectives.
22700600 Unconditional tests for comparing two ordered multinomials. 2016 Feb We consider two exact unconditional procedures to test the difference between two multinomials with ordered categorical data. Exact unconditional procedures are compared to other approaches based on the Wilcoxon mid-rank test and the proportional odds model. We use a real example from an arthritis pain study to illustrate the various test procedures and provide an extensive numerical study to compare procedures with regards to type I error rates and power under the unconditional framework. The exact unconditional procedure based on estimation followed by maximization is generally more powerful than other procedures, and is therefore recommended for use in practice.
22841964 Retinal attenuates inflammatory arthritis by reciprocal regulation of IL-17-producing T ce 2012 Nov Retinoids (e.g., vitamin A and its derivatives) can regulate immune responses. The aim of this study was to determine whether all-trans retinaldehyde (retinal), a vitamin A derivative, can inhibit inflammatory responses and joint destruction in DBA/1J mice with collagen-induced arthritis (CIA). The arthritis score and incidence of arthritis were lower in mice treated with retinal compared to those treated with cottonseed oil. Histopathologic evidence of joint damage was lower in mice treated with retinal, corresponding with a reduction in the infiltration of immune cells in mice treated with retinal type II collagen (CII)-stimulated spleen cells. In addition, the expression of proinflammatory cytokines, oxidative stress proteins, and osteoclast markers were significantly reduced in mice treated with retinal. In vitro, retinal induced increased Foxp3 expression and inhibited Th17 development. The proportion of Foxp3(+) Treg cells was increased in the spleens of mice treated with retinal, whereas the proportion of Th17 cells was reduced. In both mice and a human culture system, tartrate-resistant acid phosphatase (TRAP) positive mononuclear cells and multinucleated cells were significantly reduced after treatment with retinal. The expression of osteoclast differentiation markers was dramatically decreased upon addition of retinal. This is the first study to demonstrate the therapeutic effect of retinal on an autoimmune arthritis model in mice through reciprocal regulation of Th17 and regulatory T cells and protection of differentiation and activation of osteoclasts. Taken together, our findings indicate that retinal has profound immunoregulatory functions and potential value for the treatment of autoimmune inflammatory disorders.
22117835 Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome fro 2011 INTRODUCTION: A growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjögren's syndrome (pSS). Nonetheless, only a limited number of preclinical validation studies have been performed, limiting the possibility of translating proteomic results into clinical practice. The primary aim of this study was to refine the diagnostic power of a panel of candidate salivary biomarkers described in pSS with respect to both healthy volunteers and pathological controls. We also explored the pathogenetic function of the detected putative biomarkers both in the local exocrinopathy and in the systemic inflammatory processes of SS. METHODS: One hundred and eighty patients were included in the study overall. In the first "exploratory phase", we enrolled 40 females with pSS, 40 sex- and age-matched healthy volunteers, 10 patients with sicca non-SS and 15 secondary SS (sSS) patients. The testing cohort of the second "challenge phase" of the study was represented by 75 unselected, consecutive subjects: 19 pSS, 21 healthy volunteers, 10 sicca non-SS and 25 sSS patients. Salivary proteomic analysis was performed combining two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Western blot (WB) analysis and enzyme-linked immunosorbent assay (ELISA) were employed to validate 2DE results. Ingenuity Pathway Analysis (IPA) Knowledge base was adopted to associate candidate biomarkers in a signalling pathogenetic network. RESULTS: A total of 28, 6, 7 and 12 protein spots were found to be significantly different in pSS samples with respect to healthy volunteers, non-SS sicca syndrome, SSc-sSS and rheumatoid arthritis-sSS, leading to the identification of 15 differently expressed proteins. Among them, α-amylases precursor, carbonic anhydrase VI, β-2 microglobulin, glyceraldehydes-3-phosphate dehydrogenase (G3PDH), epidermal fatty acid binding protein (E-FABP) and immunoglobulin k light chain (IGK-light chain) apparently showed the most significant differences in pSS when compared to healthy volunteers and non-SS pathological controls. On the other hand, as expected, pSS and sSS salivary profiles shared a great number of similarities. CONCLUSIONS: This study demonstrated that salivary fluid might represent a novel ideal milieu for the detection of a diagnostic panel of candidate biomarkers for pSS, and to gain an insight into the pathogenetic processes underlying glandular and systemic autoimmune disorders.
22732856 Fatal varicella-zoster virus vasculopathy associated with adalimumab therapy. 2012 Sep OBJECTIVE: To describe the case of a patient who had been receiving adalimumab for rheumatoid arthritis and died of varicella-zoster virus vasculopathy with multifocal cerebral hemorrhage. DESIGN: Case report. SETTING: Hanyang University Hospital, Seoul, Republic of Korea. PATIENT: A 66-year-old woman with adalimumab therapy for rheumatoid arthritis followed by stuporous mental changes. RESULTS: Magnetic resonance imaging scans showed multifocal parenchymal lesions and hemorrhage in the brainstem and supratentorial areas. Polymerase chain reaction analysis of the cerebrospinal fluid was positive for varicella-zoster virus. The patient died of multifocal vasculopathy despite intensive antiviral and antibacterial medication. CONCLUSIONS: Varicella-zoster virus multifocal vasculopathy with encephalitis may be associated with adalimumab therapy. Clinicians should be aware of the possibility of fatal varicella-zoster virus vasculopathy with encephalitis in patients undergoing adalimumab therapy for rheumatoid arthritis.
22253029 Does joint position affect US findings in inflammatory arthritis? 2012 May OBJECTIVE: Musculoskeletal US is being increasingly used for the assessment of synovitis, although questions remain about its reliability. One potential factor affecting reliability is the lack of consensus of image acquisition methods such as using different joint positions. This may have an implication on the reproducibility of studies that use US as an outcome measure. The aim of this study was to determine whether a change in joint position might significantly alter the quantification of US-detected synovitis in patients with inflammatory arthritis (IA). METHODS: IA patients with clinically swollen wrists, MCP and/or knee joints were recruited. These joints were assessed quantitatively for the presence of synovitis when they were placed in different positions. RESULTS: Seventy-five patients with IA were assessed. The greatest grey scale (GS) and power Doppler (PD) scores for the MCP joints were found in the flat (0°) position (91 and 100% of cases, respectively) compared with other positions (P < 0.001). Similar results were found in the wrist joints. The greatest GS and PD scores for the knee joint were found in 30° flexion [100 and 95.6% of cases, respectively, compared with other positions (P < 0.001)]. The inter- and intra-reader reliability was good to excellent. CONCLUSION: The position in which a joint is scanned for synovitis appears to significantly influence the US assessment of synovitis. Our study suggests that the standardized scanning of the hand joints in a flat position and the knees in a 30° position are associated with the highest GS and PD scores.
20925596 Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid art 2011 May Interleukin-17A (IL-17A) is a pro-inflammatory cytokine secreted by a subset of memory T cells and other innate immune cells. It is associated with rheumatoid arthritis (RA) due to IL-17A expression in RA synovial fluid. The severe bone erosive rat adjuvant-induced arthritis (rAIA) and mouse collagen-induced arthritis (mCIA) models were used to address the therapeutic efficacy of anti-IL-17A treatment with a focused investigation on bone protection. In the rAIA model, treatment with anti-IL-17A completely alleviated arthritis, lowered the level of receptor activator of NFκB ligand (RANKL), and inhibited structural damage to the bones. In the mCIA model, IL-17A neutralization coincident with arthritis development or in mice with established arthritis diminished joint swelling by inhibiting disease initiation and progression. Intriguingly, even the few joints that became outwardly severely inflamed in the presence of an anti-IL-17A antagonist had diminished joint histopathology scores compared to severely inflamed, control-treated mice. The bone-preserving property correlated with decreased RANKL message in severely inflamed paws of arthritic mice. These data identify IL-17A as a key factor in inflammation-mediated bone destruction and support anti-IL-17A therapy for the treatment of inflammatory bone diseases such as RA.
22800927 Therapeutic effect of 7, 3'-dimethoxy hesperetin on adjuvant arthritis in rats through inh 2012 Oct In our previous study, we have demonstrated that 7, 3'-dimethoxy hesperetin (DMHP), an active derivative of hesperidin, showed pro-apoptotic effect on synoviocytes in vitro. The present study was to investigate the potential therapeutic effect of DMHP on adjuvant arthritis (AA) in rat and its possible mechanisms. Freund's complete adjuvant was used to induce AA in rats. DMHP were administered intragastrically once a day from days 12 to 21 after AA induction. Secondary paw swelling, arthritis index, and pathological assessments were observed. IL-6 production in serum and IL-6 mRNA expression in synovium was detected by ELISA and real-time RT-PCR respectively. The expression of mRNA (JAK2, STAT3) and protein (JAK2, p-JAK2, STAT3, p-STAT3) in synovium were determined. We found that DMHP significantly inhibited hind paw swelling and arthritis index, and ameliorated pathological changes of ankle joint in AA rats. DMHP suppressed the level of IL-6 in serum and the expression of IL-6 mRNA in synovium of AA rats in a dose-dependent manner. DMHP apparently decreased mRNA expression of JAK2 and STAT3 as well as protein expression of p-JAK2 and p-STAT3 in the synovium of the AA rats. Correlation analysis indicated that p-JAK2 or p-STAT3 protein expression was highly correlated with joint damage severity. In conclusion, DMHP has a powerful therapeutic effect on AA in rats and its mechanisms might be partly related to inhibiting excessive activation of JAK2-STAT3 pathway.
22049861 Prospective study of a cementless, mobile-bearing, third generation total ankle prosthesis 2011 Aug BACKGROUND: The SALTO total ankle prosthesis is a noncemented mobile bearing anatomic design characterized by dual Ti-HA coating. This study reviews our results with this prosthesis. MATERIALS AND METHODS: Between 2001 and 2007, 413 consecutive SALTO prostheses were implanted in our institution in 215 women and 198 men, aged 57.1 +/- 11.9 years. At the last visit, 401 implants (47% in the left ankle) were available with a mean followup of 29 (range, 1 to 84) months. RESULTS: Based on the results of the 218 patients with at least 2 years of postoperative followup, the 5-year estimated survivorship, with the primary end-point being implant removal, was 86.6% and ranged from 85.1% in patients with post-traumatic osteoarthritis to 95.6% in those with rheumatoid arthritis. The AOFAS score increased from 50.9 +/- 16.8 points preoperatively to 82.2 +/- 14 points at followup (mean difference, 31.1 +/- 1.4, 95% confidence interval (C.I.) for the difference, 28.3 to 33.8, p < 0.001). Visual analog scale for pain decreased from 7.4 +/- 1.1 preoperatively to 2.0 +/- 2.0 postoperatively (mean difference, -5.4 +/- 0.7, 95% C.I. for the difference, -5.6 to -5.2, p < 0.001). Flexion/extension ROM increased from 25.2 +/- 14.1 degrees to 33.1 +/- 13.6 degrees at the last followup visit (mean difference, 7.9 +/- 0.5 degrees, 95% C.I. for the difference, 4.3 to 7.2, p < 0.001), while pronation/supination ROM increased from 23.8 +/- 13.7 degrees to 25.4 +/- 14.5 degrees (mean difference, 1.6 +/- 0.7 degrees, 95% C.I. for the difference, 0.9 to 2.2, p = 0.005). CONCLUSION: The SALTO prosthesis provided good clinical and functional results and we believe helps validate the concept of anatomic replacement.
21696691 Letter: A case of generalized guttate psoriasis induced by etanercept with relapse after a 2011 Jun 15 Abatacept is the first in a new class of agents for the treatment of rheumatoid arthritis. We report a case of guttate psoriasis in a patient treated with abatacept for rheumatoid arthritis. This patient had the same reaction with etanercept in the past.
21360492 The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rh 2011 Mar OBJECTIVE: Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögren's syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime. METHODS: Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated the sex-specific lifetime risk of rheumatic disease. RESULTS: The lifetime risk of RA developing in US adults was 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor-positive RA was 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease was PMR, with a lifetime risk of 2.4% for women and 1.7% for men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men. CONCLUSION: One in 12 women and 1 in 20 men will develop an inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications regarding disease awareness campaigns.
21087862 Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR, PK/PD and 2011 Jan 1 The synthesis, structure-activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis.
22017197 Sarcoid-related uveitis occurring during adalimumab therapy. 2012 Feb PURPOSE: To report the first case of sarcoid-related uveitis in a patient receiving adalimumab. DESIGN: Case report. METHODS: A 61-year-old woman with rheumatoid arthritis treated with adalimumab for 4 years presented with a 1-year history of bilateral panuveitis with venous vasculitis and peripheral multifocal choroiditis. A small papular lesion was found on her forehead, which upon biopsy showed noncaseating granulomas. No systemic involvement was observed. RESULTS: An ophtalmological and clinical improvement was seen after (TNF) antagonist withdrawal plus a course of prednisone. CONCLUSIONS: Ophthalmologists should know that a sarcoid-like granulomatosis can develop during TNFα blockade therapy.
21905001 Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate 2012 Feb OBJECTIVE: To evaluate the efficacy and safety of treatment with ocrelizumab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and an inadequate response to MTX. METHODS: STAGE was a phase III randomized, double-blind, parallel-group international study to evaluate the safety and efficacy of ocrelizumab compared with placebo in patients with active RA continuing MTX treatment. Patients receiving stable doses of MTX were randomized to receive 2 infusions of placebo (n = 320), ocrelizumab 200 mg (n = 343), or ocrelizumab 500 mg (n = 343) on days 1 and 15 as well as weeks 24 and 26. Coprimary end points were the proportion of patients with an American College of Rheumatology 20% improvement criteria (ACR20) response at weeks 24 and 48. Secondary end points included the change from baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70 responses. RESULTS: The ACR20 response rates were 35.7% in the placebo group, 56.9% in the ocrelizumab 200 mg group, and 54.5% in the ocrelizumab 500 mg group at 24 weeks, and 27.6%, 58.3%, and 62.1%, respectively, at 48 weeks (P < 0.0001 versus placebo for each dose at both time points). At week 48, both of the ocrelizumab doses improved the ACR50 and ACR70 response rates 3-fold as compared with placebo and showed a statistically significant (P < 0.0001) reduction in joint damage progression relative to placebo (mean change in SHS reduced by 85% and 100% for the 200-mg and 500-mg doses, respectively). Rates of serious infection were comparable in the placebo (3.48 per 100 patient-years) and ocrelizumab 200 mg (3.54 per 100 patient-years) groups but were elevated in the ocrelizumab 500 mg group (8.66 per 100 patient-years). CONCLUSION: With both ocrelizumab doses, the primary end point was met, and the signs and symptoms of RA were significantly improved at weeks 24 and 48. Ocrelizumab also significantly inhibited the progression of joint damage. A higher rate of serious infections was observed with 500 mg of ocrelizumab as compared with ocrelizumab 200 mg or placebo.
21292833 American College of Rheumatology/European League against Rheumatism provisional definition 2011 Mar OBJECTIVE: Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. METHODS: A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. RESULTS: Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3. CONCLUSION: We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.
22174563 The role of T-cell leukemia translocation-associated gene protein in human tumorigenesis a 2012 Synovial tissues of patients with rheumatoid arthritis (RA) include factors regulating bone resorption, such as receptor activator NF-κB ligand (RANKL), TNF-α, IL-6, IL-17, and IFN-γ. However, in addition to these cytokines, other factors expressed in synovial tissues may play a role in regulating bone resorption. In 2009, we demonstrated that novel peptides from T-cell leukemia translocation-associated gene (TCTA) protein expressed in synovial tissues from patients with RA inhibit human osteoclastogenesis, preventing cellular fusion via the interaction between TCTA protein and a putative counterpart molecule. Only a few studies on the role of TCTA protein have been reported. Genomic Southern blots demonstrated a reduced TCTA signal in three of four small cell lung cancer cell lines, suggesting the loss of one of the two copies of the gene. In the current paper, we reviewed the roles of TCTA protein in lung cancer cell lines and human osteoclastogenesis.
22578961 Reactive oxygen species and exercise on bone metabolism: friend or enemy? 2012 Jul Reactive oxygen species (ROS) are well recognised for playing a dual role as both deleterious and beneficial species. They are normally generated by tightly regulated enzymes. ROS overproduction arises either from mitochondrial electron transport chain or excessive stimulation of NAD(P)H resulting in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures (lipids, membranes, proteins, and DNA). However, ROS could have a beneficial affect at low/moderate concentrations. Physiological roles in cellular responses to noxia have been reported, in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. The role of ROS in bone metabolism is dual. It is a key modulator of bone cell function and also implicated in the pathophysiology of mineral tissues. Elevated production of ROS and/or depletion of antioxidants have also been observed in a variety of pathological conditions, including inflammatory joint diseases. Performing physical exercise is associated with numerous health benefits, playing a role especially in the prevention of bone loss. However, the production of ROS increases during demanding exercise. To explore this further, the aim of the present review was to examine bone remodelling in relation to oxidative stress and exercise.
21190099 Three-dimensional analysis of image-free navigation system for total knee arthroplasty. 2011 Aug Malalignment causes abnormal forces that may lead to loosening after knee replacement. Whether a computer-assisted technique can improve the precision of implant positioning guaranteeing good long-term results in total knee arthroplasty, this is a matter of discussion. The authors evaluate the alignment accuracy of 20 primary total knee arthroplasties, performed using an image-free computer navigation systems, with standardized CT protocol and three-dimensional digital model reconstruction. The results of this study demonstrate that the image-free navigation system is able to improve accuracy in axial limb alignment and positioning of the components in the majority of cases; moreover, the difference between the mean mechanical axis value of the navigation system (179.7° ± 1.7°) and the median mean value obtained during the post-operative evaluation (180.3° ± 1.9°) is not statistically significant (P = 0.28).
23172753 The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in h 2013 Jul BACKGROUND: In rheumatoid arthritis (RA), neutrophil granulocytes fuel inflammation and damage tissue in the joint by releasing cytotoxic agents, antimicrobial peptides, proteases and other inflammatory mediators. The human cathelicidin LL-37 has recently been implicated in the development of systemic lupus erythematosus and psoriasis. OBJECTIVE: To elucidate if antimicrobial peptides (AMPs) contribute to the pathogenesis of arthritis. METHODS: Expression of LL-37 was determined in synovial membranes from patients with arthritis and control subjects. Expression of the rat cathelicidin rCRAMP and defensins was characterised in joints, blood and secondary lymphoid organs during pristane-induced arthritis (PIA) in rats and in a transfer model of PIA induced by CD4 T cells. Serum samples of rats with arthritis were tested for IgG and IgM autoantibodies against rCRAMP by immunoblot and for interferon (IFNα) by ELISA. RESULTS: Cathelicidins are strongly upregulated in RA synovial membranes and in joints from rats with arthritis as compared with healthy joints. Expression was most prominent in neutrophil granulocytes and macrophages/osteoclasts. Cathelicidin expression is also upregulated in the blood and spleen of pristane-injected rats, with strongest expression detected in activated CD62L- cells coexpressing granulocyte and monocyte markers. Pristane injection caused accumulation of low-density granulocytes in the blood. After pristane injection, the increased expression of rCRAMP coincided with higher levels of cell death, raised levels of interferon (IFN)α and development of autoantibodies. CONCLUSIONS: Our results show strong upregulation of cathelicidins and β-defensins coinciding with pathological events of arthritis. Higher expression and release of AMPs might contribute to development and/or maintenance of disease by systemic or local mechanisms.