scholarly journals Attenuation of Collagen-Induced Arthritis in Rat by Nicotinic Alpha7 Receptor Partial Agonist GTS-21

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yiping Hu ◽  
Ruoxi Liu ◽  
Jinchao Li ◽  
Ye Yue ◽  
Wenxiang Cheng ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Partial Agonist ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Collagen Induced Arthritis ◽  
Bone Degradation ◽  
Histological Score ◽  
Hematoxylin And Eosin ◽  
Alpha7 Receptor ◽  
Phosphate Buffered Saline

This research was performed to observe the effect of GTS-21 on Collagen Induced Arthritis (CIA). CIA model was used and after the onset of arthritis, the rats were divided into three groups based on their clinical symptoms score. Two groups were intraperitoneally (IP) injected daily with GTS-21 (1 mg/kg, 2.5 mg/kg) for a week, whereas phosphate buffered saline (PBS) was used for the control group. Cytokine titers, radiological, and histological examinations were performed at different time points after treatment with GTS-21. Compared with those of the control, the levels of TNF-α, IL-1, and IL-6 in the serum were significantly reduced after GTS-21 management. In addition, radiological results show that bone degradation was inhibited as well. Moreover, the hematoxylin and eosin (H&E) staining indicated that the histological score was significantly alleviated in the therapeutic group. Tartrate-resistant acid phosphatase (TRAP) stain-positive cells were also detected in the destruction of the articular cartilage, which was significantly reduced compared with the control group. This study provides the first evidence on the effect of GTS-21 as a potential treatment for RA.

scholarly journals SAT0018 THE THERAPEUTIC EFFECT OF STIMULATION OF THE SPLENIC NEUROVASCULAR BUNDLE IN MICE WITH COLLAGEN-INDUCED ARTHRITIS IS ENHANCED BY CONCOMITANT ANTI-TNF TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 939.2-939
Author(s):  
T. Simon ◽  
C. Panzolini ◽  
J. Lavergne ◽  
N. Hypolite ◽  
N. Glaichenhaus ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Clinical Symptoms ◽  
Pulse Amplitude ◽  
Clinical Score ◽  
Control Group ◽  
Research Support ◽  
Collagen Induced Arthritis ◽  
Etanercept Treatment ◽  
Clinical Scores ◽  
Research Grant

Background:Vagus nerve (VN) stimulation has shown the potential to improve the disease development in animal models of arthritis and in patients with RA. However, the VN can affect respiratory, cardiovascular, endocrine and gastro-intestinal physiology. The splenic nerve (SpN) has been confirmed to be the principal effector nerve for the VN-mediated immune control. Previous studies have shown that stimulating the splenic nerve resulted in an increase of norephiniphrine in the spleen, as well as a significant reduction in LPS-induced TNF (1).Objectives:To test the therapeutic efficiency of splenic nerve stimulation (SNS) in collagen-induced arthritis (CIA) in mice alone or in combination with anti-TNF treatment.Methods:CIA was induced in DBA1/J mice by immunization with bovine type II collagen at days 0 and 21. At day 11, mice were implanted with micro-cuff electrode (CorTec) onto the SpN or VN. From day 16 to day 45, SNS were applied as rectangular charged-balanced biphasic pulses with 650 μA pulse amplitude, 200 µs pulse width at 10 Hz frequency for 2 min 1 or 6 times a day using a Plexon stimulator. In order to investigatedthe mechanism of action in more detail, propranolol, a beta-adrenergic receptor (β-AR) antagonist, was added to the drinking water of mice receiving SNS. In addition, a control group was treated with anti-TNF (etanercept, 3 times/week; 10mg/kg i.p.). In curative settings, SNS and/or anti-TNF treatment was applied starting when mice scored positive for 3 consecutive days. Clinical arthritis was determined by visual examination of swelling and redness of the paws and measurement of paw thickness. Sham mice were undergoing the same procedure but did not receive stimulation.Results:In CIA in mice all sham animals developed arthritis, compared to only 14% following six times per day SNS (p <0.001) in a prophylactic setting. In contrast, 85% of the animals developed arthritis (p = 0.35) when SNS was applied only once a day. In both stimulated groups a significant decrease in clinical scores and paw thickness was observed compared to unstimulated group (p < 0.01 and p < 0.05, respectively). While etanercept treatment reduced clinical scores (p <0.001) an immediate rebound in clinical score was seen following treatment arrest, while mice with SNS were still partially protected 35 days after treatment discontinuation (p = 0.013, compared to sham). Propranolol inverted the effect of SNS in CIA mice. Finally, when SNS was applied as a curative treatment, clinical scores were significantly reduced (p < 0.001). Importantly, these clinical scores even further decreased when anti-TNF treatment was given to mice receiving SNS.Conclusion:These studies demonstrate that SNS suppresses pro-inflammatory cytokine production, and reduces clinical symptoms in mice with CIA which is at least partially mediated by the β-AR. The additive effect of anti-TNF in reducing the clinical scores demonstrates that that mechanism of action of SNS is not primarilys mediated by reducing TNF levels. Moreover, anti-TNF potentiating the inhibitory effect of SNS is supporting a combined use of these treatments, or even a combination of SNS with other biologicals, to treat RA, potentially getting more patients closer to remission. In conclusion, the data is providing compelling scientific rationale and pre-clinical evidence that splenic neuromodulation might be a new treatment modality for RA.References:[1] Guyot M et al, Brain Behav Immun. 2019;80:238.Disclosure of Interests:Thomas Simon Grant/research support from: research grant from Galvani Bioelectronics, Clara Panzolini Grant/research support from: Working on research grant Galvani bioelectronics, Julien Lavergne Grant/research support from: working on research grant Galvani Bioelectrocnics, Nicolas Hypolite Grant/research support from: Working on research grant Galvani Bioelectronics, Nicolas Glaichenhaus: None declared, Margriet Vervoordeldonk Employee of: I am an employee of Galvani Bioelectronics, Philippe Blancou Grant/research support from: Received research grant from Galvani Bioelectronics

scholarly journals The number of regulatory B cells is increased in mice with collagen-induced arthritis

2019 ◽  
Vol 14 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Li Luo ◽  
Qing Liu ◽  
Shanshan Peng ◽  
Yan Meng ◽  
Wenjing Du ◽  
...  
Keyword(s):  
B Cells ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Control Group ◽  
Synovial Cells ◽  
Regulatory B Cells ◽  
Collagen Induced Arthritis ◽  
Array Technology ◽  
Hematoxylin And Eosin ◽  
High Degree

AbstractThe aim of this study is to investigate changes in regulatory B cells (Bregs) and the expression of related cytokines such as interleukin-10 (IL-10) and transforming growth factor (TGF)-β in a mouse model of collagen-induced arthritis (CIA). A total 20 DBA/1 mice (6-8 weeks old) were randomly divided into control and CIA disease groups. For the CIA disease group, animals were injected intradermally with chicken collagen type II and complete Freund's adjuvant. The calculated arthritis index score of the CIA group was significantly higher than that in control group. Hematoxylin and eosin staining showed tumid synovial cells with irregular arrangement and obvious hyperplasia, with a high degree of inflammatory cell infiltration in CIA model group. Cytometric bead array technology and quantitative RT-PCR indicated that the levels of IL-10 and TGF-β in serum, and synovial cells were significantly increased in the CIA group. The proportion of Bregs in the spleen of the CIA group was significantly increased compared to the control group. In conclusion, our findings demonstrate that the number of Bregs and the expression of TGF-β and IL-10 are enhanced in mice with CIA.

scholarly journals Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Zhong-heng Du ◽  
Chun-wu Zhang ◽  
Wen-xia Xie ◽  
Yong Chen ◽  
Wen-jie Cong ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Peripheral Blood ◽  
Bone Erosion ◽  
Osteoclast Formation ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Collagen Induced Arthritis ◽  
Ankle Joints ◽  
Trap Staining ◽  
Adenosine A2a

Background. This study was to investigate the role of adenosine A2A receptors (A2AR) in inhibiting the effect of electroacupuncture (EA) on osteoclastogenesis in collagen-induced arthritis (CIA). Methods. Wistar rats were divided into four groups: sham-control group, CIA-control group, CIA-EA group, and CIA-EA-SCH58261 (A2AR antagonist) group. We detected tumor necrosis factor-α (TNF-α), nuclear transcription factor-κB (NF-κB), receptor activator of NF-κB ligand (RANKL), protein kinase A (PKA), and extracellular regulatory protein kinase 1/2 (ERK1/2) in peripheral blood by ELISA. PKA, ERK1/2, and NF-κB in ankle joints were determined by western blotting. We evaluated the arthritis damage by histological examination and determined the number of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining. Results. EA treatment downregulated the expression of TNF-α, RANKL, PKA, ERK1/2, and NF-κB in peripheral blood but increased the levels of PKA and ERK1/2 in ankle joints. Importantly, EA treatment reduced bone erosion as evidenced by the histological findings and inhibited osteoclastogenesis as revealed by TRAP staining. All these effects of the EA treatment were reversed by combining EA treatment with the A2AR antagonist SCH58261. Conclusion. Our data suggest that EA treatment activated A2AR. The effects of the A2AR antagonist SCH58261 suggest that the inhibition of osteoclast formation, the inhibition of TNF-α, RANKL, and NF-κB expression, and the increase of ERK1/2 are all dependent on this EA-induced A2AR activation. It is therefore likely that these pathways with clearly defined roles in inflammation and bone erosion are at least partially involved in the mediation of the inhibition of synovitis and osteoclast formation induced by EA.

Possibilities of correction of menopausal disorders in women with the use of medicine Menopace

2016 ◽  
pp. 95-100
Author(s):  
G.I. Reznichenko ◽  
◽  
N.Yu. Reznichenko ◽  
V.Yu. Potebnya ◽  
K.I. Kovalenko ◽  
...  
Keyword(s):  
General Condition ◽  
Clinical Symptoms ◽  
Average Score ◽  
Control Group ◽  
Climacteric Syndrome ◽  
Basic Subgroup ◽  
Menopausal Syndrome ◽  
Natural Menopause ◽  
Surgical Menopause ◽  
Observation Period

The objective: to determine the efficacy of medicine «Menopace» in treatment of women with natural and surgical menopause. Patients and methods. 20 women (I group) with a natural menopause were examined (basic subgroup consisted of 10 patients who used Menopace for 3 months; control subgroup consisted of 10 patients). 20 women (II group) with surgical menopause were examined (basic subgroup consisted of 10 patients who received Menopace for 3 months; control subgroup consisted of 10 patients). Results. The average score of neurovegetative and emotional manifestations of climacteric syndrome during the observation period decreased in women with natural and surgical menopause who used Menopace, compared with subgroups of patients who had not used the medicine. Conclusions. 1. The use of the medicine Menopace in women with natural menopause after 3 months showed the disappearance of clinical symptoms of climacteric syndrome in 70% of the cases, and significant improvement in general condition in 30% of cases. 2. During surgical menopause after 1 month of treatment with Menopace manifestations of sweating were observed 4.5 times less often than in control group, tides were observed 7 times less often than in control group. Neurovegetative and psychoemotional symptoms of menopause were absent in 80% of women after 3 months of treatment and in 20% of cases significant improvement was shown. 3. The obtained results give grounds to recommend wide use of Menopace in practical work for the treatment of menopausal syndrome during natural and surgical menopause. Key words: menopause, therapy, Menopace.

The Effect of Immunosuppression on Selected Antioxidant Parameters in Patients with Graves’ Disease with Active Thyroid-Associated Orbitopathy

2020 ◽  
Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudla ◽  
Jacek Karpe ◽  
Aleksandra Nowak ◽  
Mariusz Nowak
Keyword(s):  
Oxidative Stress ◽  
Clinical Symptoms ◽  
Immunosuppressive Treatment ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Graves Disease ◽  
Methylprednisolone Treatment ◽  
Antioxidant Parameters

Abstract Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.

scholarly journals Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Rajewska-Rager ◽  
Monika Dmitrzak-Weglarz ◽  
Pawel Kapelski ◽  
Natalia Lepczynska ◽  
Joanna Pawlak ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Calcium Binding ◽  
Clinical Symptoms ◽  
Small Sample Size ◽  
Serum Levels ◽  
Small Sample ◽  
Drop Out ◽  
Control Group ◽  
Longitudinal Assessment ◽  
Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

scholarly journals Implementation of NAVIGATE Coordinated Specialty Care for First Episode Psychosis: the Michigan Experience

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 177-178
Author(s):  
Eric D. Achtyes ◽  
Kari Kempema ◽  
Zhehui Luo ◽  
Katharine N. Thakkar ◽  
Catherine Adams ◽  
...  
Keyword(s):  
Mental Health ◽  
Clinical Symptoms ◽  
The United States ◽  
First Episode Psychosis ◽  
Specialty Care ◽  
First Episode ◽  
Control Group ◽  
Evidence Based ◽  
Block Grant ◽  
Episode Psychosis

AbstractStudy ObjectivesCoordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.MethodsIn 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.ResultsN=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.ConclusionThe implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.FundingSupported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

scholarly journals Clinical characteristics and outcomes of COVID-19 long-term nucleic acid positive patients

2021 ◽  
pp. 1-10
Author(s):  
Xuan Zhu ◽  
Xinxin Zhu ◽  
Min Wang ◽  
Fang Yang ◽  
Zhibing Sun ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Control Group ◽  
Viral Shedding ◽  
Imaging Characteristics ◽  
And Gender ◽  
Acid Test ◽  
Pulmonary Ct

OBJECTIVE: This study aimed to investigate the clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) long-term nucleic acid positive patients (hereinafter referred to as CLTAPs). METHODS: Patients were recruited from the Xiaogan Central Hospital between 16 January 2020 and 28 March 2020. Among the 562 cases of patients with laboratory-identified COVID-19 infection by real-time polymerase chain reaction (qtPCR), 19 cases of COVID-19 patients with more than 41 days from the first to the last time of nucleic acid test were selected as the study group, and 76 cases of age- and gender-matched COVID-19 patients were selected as the control group (hereinafter referred to as C-CLTAPs). Demographic characteristics, clinical symptoms, laboratory examination and computed tomography (CT) imaging characteristics were retrospectively analyzed. RESULTS: On admission, among the 562 cases of patients with COVID-19, there were 398 cases of ordinary COVID-19 patients, 99 cases of severe COVID-19 patients and 99 cases of critical COVID-19 patients. CLTAPs had milder clinical symptoms and longer viral shedding time in comparison to C-CLTAPs. Compared to C-CLTAPs, CLTAPs had a lower infection index at admission. CLTAPs used less oxygen therapy and a higher proportion of hydroxychloroquine treatment in comparison to C-CLTAPs. In comparison to C-CLTAPs, CLTAPs showed slower pulmonary CT progression and faster pulmonary CT absorption. CONCLUSION: In this study, out of the 562 cases, we found 19 CLTAPs. The clinical differences between CLTAPs and C-CLTAPs were compared and analyzed. We hope that these finding can provide a theoretical basis for the treatment of CLTAPs.

An Absorption Assessment of Eggshell Calcium Citrate Treated by PEF in Mice

2013 ◽  
Vol 634-638 ◽  
pp. 1413-1416 ◽  
Author(s):  
Song Yi Lin ◽  
Tong Shen ◽  
Hai Qing Ye
Keyword(s):  
Acid Phosphatase ◽  
Electric Field ◽  
Calcium Absorption ◽  
Calcium Deficiency ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Calcium Citrate ◽  
Male Mice ◽  
Normal Range ◽  
Calcium And Phosphorus

Eggshell calcium citrate (ESCC) prepared by pulsed electric field (PEF) may be a new calcium resource to help treat and prevent calcium deficiency. An absorption assessment of ESCC prepared by PEF was performed in male mice with apparent calcium absorption. Compared with control group, ESCC prepared by PEF at doses of 133.0 mg/(kg•d) significantly improved the alkalinity phosphatase (ALP) activity (P < 0.05) and decreased the levels of tartrate-resistant acid phosphatase (TRAP) (P < 0.05). The ratio of calcium and phosphorus were in the normal range. Therefore, ESCC prepared by PEF could promote the absorption of calcium in mice.

scholarly journals Berberine Delays Onset of Collagen-Induced Arthritis through T Cell Suppression

2021 ◽  
Vol 22 (7) ◽  
pp. 3522
Author(s):  
Alexandra A. Vita ◽  
Hend Aljobaily ◽  
David O. Lyons ◽  
Nicholas A. Pullen
Keyword(s):  
T Cell ◽  
Type Ii Collagen ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Preclinical Phase ◽  
T Cell Suppression ◽  
Cell Suppression ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

There is evidence that berberine (BBR), a clinically relevant plant compound, ameliorates clinically apparent collagen-induced arthritis (CIA) in vivo. However, to date, there are no studies involving the use of BBR which explore its prophylactic potential in this model of rheumatoid arthritis (RA). The aim of this study was to determine if prophylactic BBR use during the preclinical phase of collagen-induced arthritis would delay arthritic symptom onset, and to characterize the cellular mechanism underlying such an effect. DBA/1J mice were injected with an emulsion of bovine type II collagen (CII) and complete Freund’s adjuvant (day 0) and a booster injection of CII in incomplete Freund’s adjuvant (day 18) to induce arthritis. Mice were then given i.p. injections of 1 mg/kg/day of BBR or PBS (vehicle with 0.01% DMSO) from days 0 to 28, were left untreated (CIA control), or were in a non-arthritic control group (n = 15 per group). Incidence of arthritis in BBR-treated mice was 50%, compared to 90% in both the CIA and PBS controls. Populations of B and T cells from the spleens and draining lymph nodes of mice were examined on day 14 (n = 5 per group) and day 28 (n = 10 per group). BBR-treated mice had significantly reduced populations of CD4+Th and CD4+CXCR5+ Tfh cells, and an increased proportion of Foxp3+ Treg at days 14 and 28, as well as reduced expression of co-stimulatory molecules CD28 and CD154 at both endpoints. The effect seen on T cell populations and co-stimulatory molecule expression in BBR-treated mice was not mirrored in CD19+ B cells. Additionally, BBR-treated mice experienced reduced anti-CII IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement for RA, and that its effect may be mediated specifically through T cell suppression. However, the cellular effector involved raises concern for BBR prophylactic use in the context of vaccine efficacy and other primary adaptive immune responses.

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