Platelet Indices Are Associated with Disease Activity Scores and the Severity of Sacroiliitis on Magnetic Resonance Imaging in Axial Spondyloarthritis Patients

OBJECTIVE: To investigate the associations among platelet indices, disease activity scores, and inflammatory markers in axial spondyloarthritis, and to determine the relation between platelet indices and inflammation measured on magnetic resonance imaging (MRI). METHODS: The study included 161 patients who fulfilled Assessment of Spondyloarthritis International Society criteria. Platelet indices such as mean platelet volume (MPV), plateletcrit (PCT), platelet large cell ratio (PLCR), and platelet distribution width (PDW) were measured. Ninety patients underwent sacroiliac (SI) MRI at baseline. Bone marrow edema (BME) and erosion on MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and spinal radiologic progression were also assessed. The associations among platelet indices and disease activity scores and inflammatory markers were evaluated. RESULTS: Of the 161 patients, 130 (81%) were male. MPV, PLCR, and PDW were negatively associated with ASDAS and inflammatory marker expression, whereas PCT was positively associated with these parameters. MPV, PLCR, and PDW were negatively associated with BME and erosion scores on SI MRI. However, platelet indices were not associated with the BASDAI and BASFI. The mean erythrocyte sedimentation rate, C-reactive protein, and BME and erosion scores were significantly higher in patients with low MPV. Changes in MPV, PCT, and PDW at baseline and after one year were associated with changes in ASDAS and inflammatory marker expression. CONCLUSION: Platelet indices are associated with ASDAS, inflammatory marker levels, and severity of BME and erosion measured on MRI.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

Toxic Epidermal Necrolysis by Ceftriaxone in Patient with Newly Diagnosed Systemic Lupus Erythematosus

Toxic epidermal necrolysis (TEN) is a rare disease in absolute numbers with an incidence of 2 cases per million people per year. Most cases of TEN are caused by drugs, but certain infectious diseases may have an impact on the risk. There are rare reports of TEN occurring without history of drug ingestion in systemic lupus erythematosus (SLE), appearing similar to cutaneous lupus and early TEN manifestations, such as erythema multiforme. This report describes a patient with SLE who presented with manifestations of TEN after ceftriaxone treatment. The patient was newly diagnosed with SLE and TEN occurring eight days after cessation of ceftriaxone. Considering possible etiologies, we could not exclude ceftriaxone as the cause of TEN. After intravenous immunoglobulin with glucocorticoid, clinical symptoms improved.

Usefulness and Limitation of 2010 ACR/EULAR Classification Criteria in Korean Patients with Early RA

OBJECTIVE: The 2010 New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) was raised to identify patients with early RA and replaced the 1987 ACR classification criteria. The aims of this study are to assess the availability of new classification criteria and to evaluate its potential limitation. METHODS: A total of 408 patients with newly diagnosed RA were included from 13 secondary or tertiary hospitals in South Korea. The symptom duration was less than 12 months before the diagnosis of RA. RA was defined as either 1987 ACR classification criteria or new 2010 ACR/EULAR criteria. We compared the full details of both classification criteria. RESULTS: The mean symptom duration was 5.1 months. The majority (76.2%) of the patients were female. Two hundred and seventy three patients (66.9%) fulfilled both of the 2010 and 1987 classification criteria. Forty-seven (14.7%) of the 320 patients fulfilling the 1987 criteria did not fulfill the new classification criteria. On the other hand, eighty-eight (24.4%) of the 361 patients fulfilling the 2010 ACR/EULAR classification criteria did not fulfill the 1987 ACR criteria. Thirty-six (55.4%) of the 65 patient with seronegative RA failed to meet the 2010 classification criteria. In case of seropositive RA (n=343), 85 additional patients (24.8%) could be diagnosed as RA using new classification criteria. CONCLUSION: The new 2010 ACR/EULAR classification criteria enable physicians to diagnose more patients with early RA via the help of serology. However, the sensitivity for the diagnosis of seronegative RA is projected to decrease.

Induction of Remission is Difficult due to Frequent Relapse during Tapering Steroids in Korean Patients with Polymyalgia Rheumatica

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 +/- 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

Measurement of Interleukin-33 (IL-33) and IL-33 Receptors (sST2 and ST2L) in Patients with Rheumatoid Arthritis

The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 +/- 464.0 pg/mL) than in healthy controls (96.0 +/- 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1beta (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.

Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

IL-23 P19 Expression Induced by IL-17 and IL-1beta in Rheumatoid Arthritis Synovial Mononuclear Cells

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.

IL-23 P19 Expression Induced by IL-17 and IL-1beta in Rheumatoid Arthritis Synovial Mononuclear Cells

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.

Anti-CD3 Antibody Induces IL-10-producing CD4+CD25+ Regulatory T Cells, Which Suppress T Cell Response in Rheumatoid Arthritis Patients

BACKGROUND: Regulatory T cells (Tregs) have been investigated intensively for some decades. These cells regulate the immune system, prevent overactivated immune responses and can be used therapeutically. For rheumatoid arthritis (RA), understanding the functions and status of Tregs is an important step for understanding immune regulation in this autoimmune disease. METHODS: We investigated the percentages, phenotypes and suppressive functions of CD4+CD25+ Tregs in peripheral blood (PB) of patients with RA. RESULTS: The percentages were higher in the patients (n=12) than in healthy controls (n=10), and the cells expressed the CD45RBlow, CTLA-4 and CCR7 phenotypes. We also investigated the expression of Foxp3 and secretion of interleukin (IL)-10 induced CD4+CD25+ Tcells by anti-CD3 antibody treatment. A suppressive function of the patients' cells was shown through coculture with CD4+CD25+ T cells in vitro. CONCLUSION: We suggest that, despite their increased numbers and suppressive function, they manage the ongoing inflammation ineffectively. It might be possible to apply IL-10 to induce the proliferation of IL-10-producing Tregs as therapy for RA.

Clinical Characteristics of the Lung Involvement in Korean Patients with Inflammatory Myositis / 대한류마티스학회지

OBJECTIVE: To investigate the clinical manifestation and prognostic factors of interstitial lung disease (ILD) in Korean patients with idiopathic inflammatory myopathies include with polymyositis (PM) and dermatomyositis (DM). METHODS: Clinical and laboratory data of 110 patients with PM/DM in our rheumatology clinic were investigated. Clinical data including history, medication, pulmonary function tests (PFT) findings, radiologic findings, and labaratory findings were obtained from medical records at the first diagnosis of ILD with PM/DM. ILD was diagnosed on the basis of the imaging abnormalities defined above on definite findings of chest X-rays and high resolution computed tomography (HRCT), restrictive changes on PFT with respiratory symptoms. During the course of treatment, we assessed chest radiograph and HRCT findings. RESULTS: Forty-two PM/DM patients (38.2%) developed ILD. Anti-extracellular nuclear antigen (ENA) antibody, anti-Jo-1 antibody and ground glass opacity in HRCT were significantly high in PM-ILD. However honeycoomb appearance (53% : 22%) and fibrosis (41% : 6%) in HRCT were significantly high in DM-ILD. Interest in aspects of prognosis including initial steroid treatment response in HRCT were favorable in PM-ILD. There were statistically significant association between normal level of CPK and usual interstitial pneumonia (UIP) pattern in HRCT in DM-ILD. Such cases had resistance to steroid therapy. Overall interval between steroid and immunosuppressant therapy was significantly shorter in those with DM-ILD. CONCLUSION: The clinical manifestations between PM-ILD and DM-ILD in Korean patients were not significant different from those of other populations. DM-ILD is more refractory to steroid treatment, expecting in poor prognosis compared with PM-ILD. So immediate intensive immunosuppressive therapy should be considered in DM-ILD.

Thoracic CT Findings of Adult-Onset Still's Disease: A Case Report

Adult-onset of Still's disease is a rare systemic rheumatic disorder. It involves various organs including the lungs and pleura. We report here the CT findings of a patient with the thoracic manifestations of Still's disease, including axillary and mediastinal lymphadenopathies, pleural and pericardial effusions and infiltrations in both lung bases.

Reciprocal Activation of Fibroblast-like Synoviocyte and Type II Collagen-reactive T cell in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To investigate the interaction between type II collagen (CII)-reactive T cell and fibroblast-like synoviocyte in rheumatoid arthritis (RA). METHODS: Peripheral blood T cells from RA patients were cultured with bovine CII and analyzed by flow cytometry. After co-culture with CII-reactive T cells and fibroblast-like synoviocytes (FLS), the expression of cytokines (IL-15 and TNF-alpha from FLS, IFN-gamma and IL-17 from CII-reactive T cells) were determined by ELISA and RT-PCR. RESULTS: CII-reactive T cells expressed CD69, one of the early activation markers, and produced significant amount of IFN-gamma, and proliferated. IL-15 and TNF-alpha expression from FLS were significantly elevated when co-culture with CII-reactive T cells and inhibited by physical interruption of cell-to-cell contact or anti-CD40 antibody. IFN-gamma and IL-17 expression from CII-reactive T cells were also significantly elevated when co-culture with FLS and inhibited by anti-IL-15 monoclonal antibody. CONCLUSIONS: CII-reactive T cells can activate FLS to secret proinflammatoy cytokines and interactions between these two cells drive further activation of each other. These data suggest that CII-reactive T cell may play a important role in pathogenesis of RA.

Urinary Excretion of Rantes is Elevated in Lupus Nephritis / 대한류마티스학회지

OBJECTIVE: Infiltrating T cells and monocytes have been implicated in the pathogenesis of lupus nephritis (LN). Chemokines may play a key role in the recruitment of these cells. We investigated whether RANTES (regulated on activation normal T cell expressed and secreted), one of the CC chemokine family, may be involved in the pathogenesis of LN. METHODS: We measured the levels of RANTES in sera and urine from 87 systemic lupus erythematosus (SLE) patients and 78 healthy controls using ELISA. Clinical and laboratory assessment including SLE disease activity index (SLEDAI) were performed at the time of sampling. RESULTS: Serum RANTES levels were significantly higher in the patients with SLE than in healthy controls (115.0+/-5.6 vs. 91.5+/-4.0 pg/ml, p=0.001, mean+/-SEM). Serum RANTES levels correlated well with anti-dsDNA antibody titer (r=0.29, p<0.05) and inversely with serum complement C4 level (r=-0.28, p<0.05). Urinary RANTES/creatinine ratios were significantly higher in patients with nephritis than those without (3.4+/-0.4 vs. 2.2+/-0.3, p=0.004), while serum RANTES level was not different between patients with nephritis and those without. Moreover, urinary RANTES/creatinine ratio positively correlated with urine protein/creatinine ratio (r=0.41, p<0.001). CONCLUSIONS: Our results demonstrate that serum RANTES was elevated in patients with SLE and urinary excretion of RANTES was strongly associated with presence of nephritis. These data suggest that RANTES may be expressed in renal inflammatory sites and may participate in the pathogenesis of LN possibly by augmenting the recruitment of T cells and monocytes.

Disorders of the Shoulder Region / 대한내과학회지

No abstract available.

Effects of Rebamipide Against Nonsteroidal Anti-inflammatory Drugs (NSAIDs)Induced Gastroduodenal Mucosal Injury / 대한류마티스학회지

OBJECTIVES: To investigate protective effect of rebamipide against nonsteroidal anti-inflammatory drugs (NSAIDs)induced gastroduodenal mucosal injury. METHODS: Randomized eight patients with rheumatic disease starting NSAIDs underwent pre-treatment gastroduodenoscopy,and degree of mucosal injury and several gastrointestinal (GI)symptoms were graded by Lanza score scale (rating from 0 to 4)and symptom score scale (rating from 0 to 3).Eight weeks after the subjects had received concomitant rebamipide 100mg bid and NSAIDs they underwent post-treatment gastroduodenoscopy and degree of mucosal injury and GI symptoms were graded.Randomized previous NSAIDs-used 20 patients with rheumatic disease were also investigated.Eight weeks after 100mg bid with concomitant NSAIDs,they underwent gastroduodenoscopy and degree of mucosal injury and GI symptoms were graded. RESULTS: All eight patients who received concomitant rebamipide and NSAIDs had no interval changes between pre and post-treatment mucosal injury scores and had little interval changes between pre and post-treatment symptom scores. In previous NSAIDs-used patients with rheumatic disease,incidence of each gastric ulcer and duodenal ulcer were 16.7%and 11.1%and all mean symptom scores were lower than 1.0.No special adverse effect was developed during the study. CONCLUSION: Rebamipide seems to have a good protective effect against NSAIDs induced mucosal injury and GI symptoms and probably have rare adverse effect.

A Case of Relapsing Polychondritis Associated with Sjogren's Syndrome / 대한류마티스학회지

Relapsing polychondritis is a rare multisystem rheumatic disease,characterized by recurrent and potentially destructive inflammatory lesions of cartilaginous structures.All types of cartilage & other proteoglycan-rich structures may be involved,resulting in auricular chondritis,laryngotracheal chondritis,ocular symptoms,vasculitis,cardiac abnormalities,skin lesions and glomerulonephritis. The disease may be associated with another connective tissue and autoimmune diseases such as rheumatoid arthritis,systemic lupus erythematosus,Sjogren's syndrome and systemic vasculitis. We experienced a 69-year-old female patient who had been previously diagnosed as Sjogren's syndrome,presenting respiratory tract involvement,episcleritis,auricular chondritis and vestibular dysfunction.

Tolerogenic Effect of Orally Administrated Type II Collagen in CIA Animal (DBA/1 mice) / 대한류마티스학회지

OBJECTIVE: To investigate the dosage of bovine type II collagen (BnCII) for the induction of oral tolerance in CIA animals, and to verify the changes of immune response and TGF-beta production of mesenteric lymph node cells in tolerized CIA animals. METHODS: Oral tolerance was induced by feeding of variable doses (5 microgram, 10 microgram, 20 microgram and 40 microgram) of BnCII to DBA/1 mice 4 times per week during 2 weeks, and control mice were given ovalbumin (1000 microgram), before immunization. We examed clinical assessment ; incidence of arthritis, severity of arthritis, arthritic limb by visual analysis. IgG antibodies to BnCII were measured by ELISA, T cell responses to BnCII and PHA were quantified by antigen (CII)-induced 3H-thymidine incorporation into lymphocytes of mesenteric lymph node, draining lymph node, and spleen. TGF-beta in supernatants obtained from lymph node culture medium was measured by ELISA. RESULTS: Arthritis limbs were observed in 100% of control at 5 weeks after subcutaneous BnCII injection. The incidences of CIA in all tolerized group were significantly lower than that in control 5 weeks after immunization (control 100 % vs. 5 microgram feeding group: 50%, 10 microgram feeding group: 50%, 20 microgram feeding group: 50%, 40 microgram feeding group: 55.5%, P<0.01). In comparison to control, mean articular indices were lower in all tolerized groups (control 5.13 : 5 microgram feeding group 3.50, 10 microgram feeding group 2.75, 20 microgram feeding group 2.87, 40 microgram feeding group 2.63, P<0.05). Arthritic limbs were also significantly lower in tolerized groups (control 58.3 : 5 microgram feeding group 20.8, 10 microgram feeding group 16.7, 20 microgram feeding group 20.8, 40 microgram feeding group 20.8, P<0.05). The titers of IgG antibody to CII were lower in tolerized group than that in control [tolerized group ; median 10 (min. 0, max. 48), control ; median 33 (min. 8.6, max. 101), P<0.05]. The proliferative responses to BnCII were significantly suppressed in tolerized (control 8010+/-2319cpm, tolerized group 4500+/-2060cpm, P<0.01). High TGF-beta production was noted in tolerized group (control ; 28pg/ml, BnCII feeding group ; 73pg/ml). CONCLUSION: Oral tolerance in DBA/1 mice was successfully induced from low doses of BnCII (5 microgram) and suppressed T and B cell function in conjunction with increased TGF-beta production may play an important role for the induction of CII induced oral tolerance in DBA/1 mice.

Tolerogenic Effect of Orally Administrated Type II Collagen in CIA Animal (DBA/1 mice) / 대한류마티스학회지

OBJECTIVE: To investigate the dosage of bovine type II collagen (BnCII) for the induction of oral tolerance in CIA animals, and to verify the changes of immune response and TGF-beta production of mesenteric lymph node cells in tolerized CIA animals. METHODS: Oral tolerance was induced by feeding of variable doses (5 microgram, 10 microgram, 20 microgram and 40 microgram) of BnCII to DBA/1 mice 4 times per week during 2 weeks, and control mice were given ovalbumin (1000 microgram), before immunization. We examed clinical assessment ; incidence of arthritis, severity of arthritis, arthritic limb by visual analysis. IgG antibodies to BnCII were measured by ELISA, T cell responses to BnCII and PHA were quantified by antigen (CII)-induced 3H-thymidine incorporation into lymphocytes of mesenteric lymph node, draining lymph node, and spleen. TGF-beta in supernatants obtained from lymph node culture medium was measured by ELISA. RESULTS: Arthritis limbs were observed in 100% of control at 5 weeks after subcutaneous BnCII injection. The incidences of CIA in all tolerized group were significantly lower than that in control 5 weeks after immunization (control 100 % vs. 5 microgram feeding group: 50%, 10 microgram feeding group: 50%, 20 microgram feeding group: 50%, 40 microgram feeding group: 55.5%, P<0.01). In comparison to control, mean articular indices were lower in all tolerized groups (control 5.13 : 5 microgram feeding group 3.50, 10 microgram feeding group 2.75, 20 microgram feeding group 2.87, 40 microgram feeding group 2.63, P<0.05). Arthritic limbs were also significantly lower in tolerized groups (control 58.3 : 5 microgram feeding group 20.8, 10 microgram feeding group 16.7, 20 microgram feeding group 20.8, 40 microgram feeding group 20.8, P<0.05). The titers of IgG antibody to CII were lower in tolerized group than that in control [tolerized group ; median 10 (min. 0, max. 48), control ; median 33 (min. 8.6, max. 101), P<0.05]. The proliferative responses to BnCII were significantly suppressed in tolerized (control 8010+/-2319cpm, tolerized group 4500+/-2060cpm, P<0.01). High TGF-beta production was noted in tolerized group (control ; 28pg/ml, BnCII feeding group ; 73pg/ml). CONCLUSION: Oral tolerance in DBA/1 mice was successfully induced from low doses of BnCII (5 microgram) and suppressed T and B cell function in conjunction with increased TGF-beta production may play an important role for the induction of CII induced oral tolerance in DBA/1 mice.