Fusen herbal tea influenced of spleen deficiency rats model

Influence of spleen deficiency rat model to observe the Fusen herbal tea.MethodsRats were gavaged 15% rhubarb powder suspension (5 mL) of 17 days, twice a day. It caused by the spleen deficiency rats model, rats model are respectively at the same time drinking large doses of Fusen herbal tea, a small dose of Fusen herbal tea, a high dose of Wang Laoji herbal tea, a small dose of Wang Laoji herbal tea. When modeling will replace the corresponding tea rat normal blank group were given normal drinking water instead of daily water, and Baohewan group given a pill solution. In the 17 days, Rats were killed and observe the changes of rats.ResultsRat model were successded in spleen deficiency. The pathological changes of the organs in the model group, the pathological changes of the organs in the model group, but every dose of Fusen herbal tea has no obvious effect on rats.ConclusionFusen herbal tea has no obvious effect on rats.     

胶原诱导型关节炎大鼠的关节影像学特点

目的旨在分析CIA X线片四肢关节的破坏特点,揭示CIA大鼠关节破坏的规律,为规范评分方案提供依据。方法采用П型胶原和弗氏完全佐剂皮下注射清洁级Wistar大鼠,造模成功（每批10只,共3次）后第35天行全身X线钼靶照片,以正常组作为对照、每只大鼠评价96块骨破坏（erosion）和100个关节间隙（joint space narrowing,JSN）;处死动物,取左前肢和右后肢近端第3足趾关节苏木素-伊红（HE）染色,评价中性粒细胞、淋巴细胞、浆细胞浸润、滑膜增生和软骨破坏的情况。结果造模成功后CIA大鼠关节出现明显的红肿,活动受限;HE病理显示,CIA关节存在明显的中性粒细胞、淋巴细胞和浆细胞浸润,滑膜增生,纤维组织增生,软骨破坏;X线片分析结果显示：①广泛性骨质疏松,边缘性骨质侵蚀,关节间隙狭窄或增宽,部分踝关节间隙消失,关节相互融合甚至骨性强直。②67%的骨出现erosion,JSN影响为78%,关节破坏以中、重度为主;③远端、近端趾间关节和踝关节发病率高,损害严重,掌趾关节发病率低,破坏较轻。④后肢关节破坏重于前肢（P〈0.01）,左右肢没有显著性差异（P〉0.05）。结论①滑膜是CIA炎症反应启动的主要病灶,与骨交界的滑膜和血管翳造成了CIA的骨质破坏;②CIA影像学表现关节破坏严重,以远端、近端趾间关节和踝关节为主,这些关节可作为评价破坏程度的选择。本研究对于深入CIA关节破坏的病因病理和进一步规范X线片评分方案具有一定意义。     

Histopathological study of arthritic lesions induced by immunization with type II collagen in DBA/1J mouse

Eight male DBA/1J mice immunized twice by intradermal injection of type II collagen were autopsied 12 weeks after the first immunization and analyzed for anti-type II collagen antibody level, and the limb joints were examined radiologically and histopathologically. Clinical onset of swelling and erythema in the limb joints occurred about 5 weeks after the first immunization and deformity of the limbs was observed in a few animals about 5 weeks later. Although there were marked individual differences, serum anti-type II collagen antibody levels were elevated in all animals. Histopathologically, the changes were similar to those seen in human rheumatoid arthritis and were characterized by proliferation of synovial lining cells, formation of granulation tissue with destruction of cartilage and subchondral bone, and ankylosis. Systematic examination of various joints of the fore- and hind-limbs revealed definitely that the sequence of arthritic lesions was not uniform. The knee joint was involved most frequently, but smaller joints such as the phalangeal joints were involved less frequently but exhibited severe changes. The significance of histopathological examinations in the evaluation of effects of anti-rheumatic drugs was discussed with reference to this model.     

Production of murine collagen-induced arthritis using Klebsiella pneumoniae O3 lipopolysaccharide as a potent immunological adjuvant.

Collagen-induced arthritis (CIA) was produced in mice with non H-2q and H-2r haplotypes by repeated immunization of porcine type-II collagen (CII) together with Klebsiella O3 lipopolysaccharide (KO3 LPS) as an immunological adjuvant. Histological changes that appeared in joints of repeatedly immunized mice were characterized by destruction of normal joint structure, synovial hyperplasia with proliferation of synovial cells, and infiltration of inflammatory cells. No such lesions were produced in mice receiving repeated injections of CII alone or KO3 LPS alone. Development of the humoral antibody and the delayed-type hypersensitivity to CII was exclusively found in mice immunized with the mixture of CII and KO3 LPS. It was therefore suggested that arthritis lesions induced by repeated immunization with the mixture of CII and KO3 LPS might be caused by an autoimmune mechanism, and that the experimental model might be useful for characterization of human rheumatoid arthritis (RA).     

Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats

To evaluate the antioxidant activity of the glycosaminoglycans hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S), we used a rat model of collagen-induced arthritis (CIA). Arthritis was induced in Lewis rats by multiple intradermal injections of 250 μl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail and into three to five other sites on the back. Rats were challenged again with the same antigen preparation 7 days later. Disease developed about 11 days after the second immunization. The effects of treatment in the rats were monitored by biochemical parameters and by macroscopic and histological evaluations in blood, synovial tissue and articular cartilage. Arthritis produced the following symptoms: severe periarticular erythema, edema and inflammation in the hindpaws; membrane peroxidation in the cartilage of the joints; endogenous antioxidant wasting; high tumour necrosis factor-α (TNF-α) plasma levels; and synovial neutrophil accumulation. Treatment with HYA and C4S, starting at the onset of arthritis for 10 days, limited the erosive action of the disease in the articular joints of knee and paw, reduced lipid peroxidation, restored the endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase, decreased plasma TNF-α levels, and limited synovial neutrophil infiltration. These data confirm that erosive destruction of the joint cartilage in CIA is due at least in part to free radicals released by activated neutrophils and produced by other biochemical pathways. The beneficial effects obtained with the treatment suggest that HYA and C4S could be considered natural endogenous macromolecules to limit erosive damage in CIA or as a useful tool with which to study the involvement of free radicals in rheumatoid arthritis.     

Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases.Abbreviations: μCT, microCT, CIA, collagen-induced arthritisArthritis is among the most common diseases in both children and adults. In children, growth, hormonal changes, and neuroimmune responsiveness and plasticity might confer influences on arthritic processes not seen in adults. Age-dependent outcomes have been demonstrated by using animal models of osteoarthritis;^5,6,11 however, there is limited information about how pathogenic processes vary among different age groups with experimental inflammatory arthritis in general^7,10 and in the collagen-induced arthritis (CIA) model of arthritis in particular.⁸ Studying and comparing features of the CIA model in growing compared with mature rats can be undertaken in ways that are not possible in humans and could help to understand age-related pathologic differences in children and adults with inflammatory joint diseases. Therefore, we undertook to compare clinical and imaging features of CIA in juvenile (growing) compared with young adult (mature) rats.In some animal models, collagen immunization results in a monophasic, polyarticular, inflammatory arthritis that is mediated by an autoimmune response¹⁴ and that is histopathologically similar to rheumatoid arthritis.^3,9,13 CIA predominantly affects the peripheral appendicular joints and is characterized by intense synovitis and pannus formation, with consequent erosions of cartilage and subchondral bone.^12,15Here we report that juvenile and young adult rats differ in their clinical responses to collagen immunization and that, according to findings from microCT (µCT) and ultrasonography, juvenile and young adult rats differ in their responses to collagen immunization with regard to disease pathology.     

Effect of Brand's glucosamine with essence of chicken on collagen-induced arthritis in rats

The anti-arthritic effects of glucosamine incorporated in a chicken-meat extract known as Brand's Glucosamine with Essence of Chicken versus glucosamine or Essence of Chicken (EOC) alone were investigated on collagen induced arthritis (CIA) in dark agouti (DA) rats. Four groups of rats received basic food (control), 1.2% glucosamine (GLU), 0.8% EOC and 1.2% GLU + 0.8% EOC (GLU + EOC) admixed with basic food for 25 days following CIA. Foot pads were isolated on day 25 for histopathological evaluation. Clinical assessment of hind paw swelling as measured by foot pad volumes and histopathological scoring based on the degree of edema, periosteal new bone formation, periostitis and inflammatory cell infiltration of the isolated foot pad were performed. Arthritic rats given GLU + EOC showed significant reduction in left hind paw swelling following onset of arthritis. Correspondingly, a lesser degree of edema, periosteal new bone formation, periostitis and inflammatory cell infiltration was seen in histological sections of the left hind foot pads of these rats. A similar trend of reduced hind paw swelling was observed in the right hind paws of the same rats and those fed with EOC. Rats fed with GLU alone did not demonstrate these beneficial effects. The present findings demonstrate that a combination of glucosamine and EOC is effective in reducing the histopathological severity of arthritis, probably due to its ability to reduce the inflammatory conditions in CIA.     

Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat.

The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney.     

Morphological and histopathological changes in tongues of experimentally developed acromegaly-like rats.

An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological tongue changes and clarify whether the changes were reversible. Human recombinant IGF-I (640 microg/day) was continuously subcutaneously infused into ten-week-old male rats for four weeks (IGF-I group; n = 6). Control sham-operated animals were injected saline alone (control group; n = 6). Rats were sacrificed immediately on ending administration at the age of fourteen weeks. Another 12 rats (6 from each group) were housed for an additional four weeks after administration ended. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. Tongue weights significantly increased with histopathological changes present (increases in the muscle-bundle width, spaces between muscle-bundles and epithelium thickness) in the IGF-I group compared to control rats. Tongue size returned to control levels after discontinuation of IGF-I administration. These findings suggest that the characteristic tongue enlargement was developed experimentally in our acromegaly-like rat model, and that such morphological and histopathological tongue changes are reversible on normalization of circulating IGF-I levels.     

Attenuation of collagen arthritis and modulation of delayed-type hypersensitivity by type II collagen reactive T-cell lines

T-cell lines were established from the lymph node cells of syngeneic Louvain (LOU) rats previously immunized with native chick type II collagen (CII) emulsified in incomplete Freund's adjuvant. The CII lines proliferated in vitro to type II collagen but not to type I collagen, ovalbumin (OV), or PPD. Control lines, developed from LOU rats immunized with OV emulsified in complete Freund's adjuvant, were OV specific because they did not respond to other antigens in vitro. CII line cells could adoptively transfer delayed-type hypersensitivity (DTH) but did not induce IgG antibody production to collagen. Moreover, the intravenous administration of 2 X 10(7) CII line cells prevented the subsequent induction of collagen arthritis following immunization and suppressed DTH to collagen without affecting antibody responses in the recipients. Spleen cells, but not sera, from these resistant rats decreased CII line reactivity in vitro. OV or irradiated CII lines had no effect on clinical or immunologic parameters in this model. These findings demonstrate protection from arthritis afforded by T-cell line transfer and suggest that the phenomenon results from down-regulation of the recipients' cellular immunity to collagen.     

Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.     

Suppression of collagen arthritis with antibodies to an arthritogenic, oligoclonal T cell line.

Rats immunized with type II collagen (CII) develop an immunologically mediated polyarthritis. T cells have been implicated in the pathogenesis of this model since they can adoptively transfer the disease. A CII-specific T cell line (VA), consisting of three distinct clones by Southern blot analysis, has been shown to be arthritogenic. Antibodies specific for this line were generated by immunizing rabbits. In an attempt to prevent collagen-induced arthritis (CIA), Louvain rats were injected with 1 ml of anti-VA ip on Days -1, +1, +3 and 0.5 ml on Day +5 (early treatment). To evaluate its effect on existing disease, rats received anti-VA on the day of arthritis onset and subsequently on 4 successive alternate days using the same dosage protocol (late treatment). Control rats received no therapeutic injections or were administered normal rabbit serum. All rats were immunized with CII on Day 0 to induce CIA. Rats administered antibodies using the early anti-VA treatment protocol had a significantly diminished incidence of arthritis compared to controls. Established arthritis was significantly diminished compared to controls in rats given the late anti-VA treatment. In both protocols, radiographic evidence of joint destruction was significantly reduced compared to controls. T cell phenotyping using flow cytometry analysis demonstrated that the anti-VA antibody therapy selectively eliminated a small subset of T cells since there was little difference in total T cell counts in the experimental versus control groups. Delayed type hypersensitivity and IgG antibody titers to CII were minimally decreased in the experimental versus control group. These results suggest that antibodies raised to an oligoclonal arthritogenic T cell line can suppress collagen arthritis. This may have implications with respect to 1) the size of the T cell receptor repertoire involved in the pathogenesis of collagen arthritis and 2) immunospecific protocols for CIA and other autoimmune diseases.     

A theoretical model of enlarging intracranial fusiform aneurysms

The mechanisms by which intracranial aneurysms develop, enlarge, and rupture are unknown, and it remains difficult to collect the longitudinal patient-based information needed to improve our understanding. We submit, therefore, that mathematical models hold promise by allowing us to propose and test competing hypotheses on potential mechanisms of aneurysmal enlargement and to compare predicted outcomes with limited clinical information--in this way, we may begin to narrow the possible mechanisms and thereby focus experimental studies. In this paper, we present a constrained mixture model of evolving thin-walled, fusiform aneurysms and compare multiple competing hypotheses with regard to the production, removal, and alignment of the collagen that provides the structural integrity of the wall. The results show that this type of approach has the capability to infer potential means by which lesions enlarge and whether such changes are likely to produce a stable or unstable process. Such information can better direct the requisite histopathological examinations, particularly on the need to quantify collagen orientations as a function of lesion geometry.     

胶原性关节炎大鼠炎性细胞因子的动态观察

目的通过对胶原性关节炎(CIA)大鼠多个细胞因子的动态观察,了解其变化规律,为阐明RA发病机制及CIA大鼠的模型研究提供实验依据。方法建立CIA大鼠模型。分别于初次免疫后第0、10、20、30、40、50、60天记录大鼠的体重,测量大鼠后足体积和足垫厚度,计算关节炎指数;HE染色光镜下观察关节滑膜病理变化;采用ELISA方法检测大鼠血清中TNF-α、IL-1β和IL-6水平变化。结果造模成功后的CIA大鼠14 d左右出现炎症反应,30 d左右达高峰,以后炎症逐渐减轻。与同期空白对照组大鼠相比,CIA大鼠血清中TNF-α水平10 d明显升高(P<0.01),IL-1β和IL-6水平20 d明显升高(P<0.05),三者水平均30 d达高峰(P<0.01),以后持续存在,但水平有所降低。结论 CIA大鼠血清中TNF-α、IL-1β和IL-6在RA的整个病程中一直发挥着重要作用。     

Allylpyrocatechol attenuates methotrexate-induced hepatotoxicity in a collagen-induced model of arthritis

The cornerstone of treatment for rheumatoid arthritis is low dose methotrexate (MTX), but its use is limited by concerns regarding its potential for hepatotoxicity. Allylpyrocatechol (APC), a phytoconstituent sourced from leaves of Piper betle demonstrated antioxidant, anti-inflammatory, and antiarthritic properties. The present study aimed to evaluate the combined effect of APC and MTX on limiting progression of lipopolysaccharide accelerated collagen-induced arthritis, along with reduction of MTX-induced hepatic damage. A collagen-induced arthritis (CIA) model was established by immunising Sprague-Dawley rats with bovine collagen type II (CII) and lipopolysaccharide, followed by a booster dose of CII on day 15. Rats from days 11–27 were administered APC (20?mg/kg), methotrexate (1.5?mg/kg), or a combination of MTX and APC. The combinatorial therapy of APC and MTX significantly improved the parameters of arthritis as evident from the reduction in paw oedema and arthritic score and was endorsed by radiological and histopathological changes. This combination prevented the rise in levels of proinflammatory cytokines, tumour necrosis factor (TNF-α), and interleukin 6 (IL-6). Furthermore, unlike MTX-monotherapy, the APC-MTX combination decreased the associated cachexia, splenomegaly, and oxidative stress. Importantly, the hepatic damage mediated by MTX monotherapy was effectively attenuated by the inclusion of APC. Taken together, antioxidants such as APC when combined with MTX not only potentiated the antiarthritic effect but importantly alleviated the MTX-induced hepatic damage, thus endorsing its effectiveness in preventing progression of articular diseases such as rheumatoid arthritis.     

Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 1. Dependence on dose and severity threshold.

The effects of human recombinant interleukin-1 beta (HrIL-1 beta) were investigated in arthritic rats sensitized with type II collagen (CII) and muramyl dipeptide (MDP). When administered subcutaneously (sc) daily during established arthritis, low (0.02 micrograms) and medium (0.2 micrograms) HrIL-1 beta doses exerted paradoxical beneficial properties on paws with moderate and severe inflammation, respectively. In contrast, the highest dose (2 micrograms) had a pejorative effect on developing arthritis. In addition, HrIL-1 beta attenuated paw volume and deterioration of the joints as assessed radiologically. Hence, paw inflammation response to IL-1 exposure depended on the dosage and the severity of previous arthritis prior to the IL-1 challenge. Some of these paradoxical activities may be due to the capacity of IL-1 to induce its own inhibitors or feedback loops thus counterbalancing its phlogistic properties.     

Alterations of thymic morphology and antioxidant biomarkers in 60-day-old male rats following exposure to a continuous 900 MHz electromagnetic field during adolescence

We investigated changes in thymic tissue of male rats exposed to a 900 megahertz (MHz) electromagnetic field (EMF) on postnatal days 22–59. Three groups of six 21-day-old male Sprague-Dawley rats were allocated as: control (CG), sham (SG) and EMF (EMFG) groups. No procedure was performed on the CG rats. SG rats were placed in a Plexiglas cage for 1 h every day between postnatal days 22 and 59 without exposure to EMF. EMFG rats were placed in the same cage for the same periods as the SG rats and were exposed to 900 MHz EMF. Rats were sacrificed on postnatal day 60. Sections of thymus were stained for histological assessment. Oxidant/antioxidant parameters were investigated biochemically. Malondialdehyde (MDA) levels in EMFG increased compared to the other groups. Extravascular erythrocytes were observed in the medullary/corticomedullary regions in EMFG sections. We found that 900 MHz EMF applied for 1 h/day on postnatal days 22–59 can increase tissue MDA and histopathological changes in male rat thymic tissue.     

Collagen autoimmunity and arthritis

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen-induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.     

Protocol for the induction of arthritis in C57BL/6 mice

Collagen-induced arthritis is a well-validated, but strain-dependent mouse model of rheumatoid arthritis, with H-2(q) and H-2(r) strains showing the greatest degree of susceptibility. This protocol describes the induction of arthritis in the C57BL/6 strain (H-2(b)), which forms the genetic background of the majority of genetically modified strains. This protocol involves purification of type II collagen from chicken sternums, immunization of mice, clinical assessment of arthritis and analysis of T- and B-cell responses to type II collagen. Key aspects of the protocol are the need to use chicken collagen for immunization and the importance of avoiding aggressive behavior in males. The incidence of arthritis varies from 50 to 80% and is milder than the classical collagen-induced arthritis model. This procedure takes approximately 3 months to complete.     

HLA-DR2-associated Dw subtypes correlate with RFLP clusters: most DR2 IDDM patients belong to one of these clusters

The incidence of arthritis and the antibody response to mouse and to rat type 11 collagen after immunization with native rat type II collagen was studied in different mouse strains, including wild mouse-derived strains belonging to the H-2^p/H-2^q family. High serum levels of antibodies to mouse and rat type II collagen were seen only in H-2^q mice, whereas mice belonging to the p, w3, w5, and w17 haplotypes displayed low type II collagen-specific antibody responses. Mice from three different H-2^q-carrying strains (DBA/1, NFR/N, and B10.G) with different non-major histocompatibility complex genes were all susceptible to collagen arthritis, but they displayed a varying incidence of arthritis and varying clinical features. No arthritis was seen in non-H-2^q mice, except in the B10.CAS2 strain where a few mice developed arthritis despite very low serum levels of type II collagen-specific antibodies. We conclude that small differences in the A chain of class II transplantation antigens are of importance for the development of arthritis and for the stimulation of a high response after immunization with type 11 collagen.Abbreviations used in this paper ELISA enzyme-linked immunosorbent assay - PBS phosphate-buffered saline - Ig immunoglobulin - MHC major histocompatibility complex