Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether native bovine type XI collagen (BXI) is arthritogenic, five strains of inbred mice were immunized with BXI/CFA. Arthritis was not observed in any of these strains, though it was prevalent in DBA/1 and B10.RIII controls immunized with bovine type II collagen (BII). Antisera from BXI-immunized mice reacted with mouse type XI collagen (MsXI), weakly with the alpha-chains of BXI, and minimally with mouse type II collagen (MsII). However, antisera to BII reacted with MsII and MsXI, indicating antibodies to conformation-independent epitopes shared by alpha 1(II) and alpha 3(XI). Mice immunized with BXI containing a small amount of BII developed arthritis much like those immunized with BII; sera from these mice reacted with MsXI and MsII. Delayed-type hypersensitivity responses differed from IgG responses, i.e., BXI elicited responses to alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II); BII, to alpha 3(XI) and alpha 1(II) exclusively. To determine whether alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II) are arthritogenic, DBA/1J mice were immunized with each alpha-chain. Arthritis was seen in mice injected with alpha 3(XI) or alpha 1(II). Sera to both alpha-chains reacted similarly with MsII and peptide fragment alpha 1(II)-CB11. Epitope mapping using polyclonal and mAb to type II collagen revealed that all polyclonal and 11 of 14 mAb reacted with alpha 3(XI) and alpha 1(II), whereas three mAb reacted only with alpha 1(II). In conclusion, BXI is immunogenic but not arthritogenic in five strains of mice, whereas alpha 3(XI) and alpha 1(II) are arthritogenic and immunogenic in DBA/1 mice and share greater than or equal to 11 epitopes recognized by autoantibody.
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PMID:Immunity to type XI collagen in mice. Evidence that the alpha 3(XI) chain of type XI collagen and the alpha 1(II) chain of type II collagen share arthritogenic determinants and induce arthritis in DBA/1 mice. 171 Feb 40

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
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PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
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PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

In an attempt to evaluate the role of IFN-gamma in autoimmune arthritis, we tested the effects of IFN-gamma and anti-IFN-gamma mAb (DB-1) in various phases of arthritis development in a rat model for rheumatoid arthritis; the adjuvant arthritis (AA) model, induced by immunization with CFA. In addition, the effects of IFN-gamma were tested in vitro on T cell clones derived from rats afflicted with AA. T cell clone A2b, which has been shown to be arthritogenic secreted low amounts of IFN-gamma and its Ag-specific proliferation was inhibited by IFN-gamma. In contrast, clone A2c, which can inhibit the development of AA, produced high amounts of IFN-gamma and its proliferation was increased by IFN-gamma. In vivo administration of IFN-gamma 24 h before CFA caused an enhancement of arthritis, whereas giving IFN-gamma 24 to 48 h after CFA suppressed the disease. Administration of IFN-gamma between day +4 to +12 or between day +12 to +24 increased the severity of the first phase of the disease, but had no effect later. Administration of DB-1 1 to 2 days before adjuvant or between day +4 to +8 substantially decreased the disease, whereas DB-1 given from day +12 to +24 significantly enhanced it. Taken together, these results illustrate the heterogeneity of IFN-gamma in autoimmune arthritis and suggest a rational explanation for the possibly conflicting reports regarding the role(s) and effects of IFN-gamma in autoimmune processes. The multistage nature of T cell-mediated autoimmune arthritis may be due to the predominance of distinct T cell populations at different stages of the disease. The differences in the biologic activities of these T cells may be due to their patterns of lymphokine production.
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PMID:Heterogeneous effects of IFN-gamma in adjuvant arthritis. 249 48

An evocation of arthritis by an Ag-specific lymphokine has recently been considered with the description of arthritogenic factor (AF) in rats with collagen arthritis. Because rats with CFA-induced arthritis also exhibit T cell reactivity to native type II collagen, T cell lines specific for this protein were established from CFA-injected rats. Supernatant material from these lines contained a type II collagen-binding lymphokine with functional and biochemical attributes identical with those described for AF, i.e., it was a 65-kDa species cross-reacting immunoprotein possessing the ability to incite an erosive, proliferative synovitis when injected into the knee joint of naive recipients. Similarities were also observed with HPLC and on two-dimensional gels. Lymph node cells from rats with arthritis created by injection of the synthetic adjuvant, CP-20,961 failed to produce AF, suggesting that this material is not a ubiquitous concomitant of inflammatory arthritis in the rat. Test injections into sites contiguous with the ear cartilage plate and into fibroblast-lined s.c. pouches suggested that cartilage was a requisite for the induction of inflammation by AF. These data identify a potentially shared effector pathway in the collagen and adjuvant models. The presence of AF in two frequently used models further supports the hypothesis that Ag-specific lymphokines can create autoimmune disease.
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PMID:Detection of arthritogenic factor in adjuvant arthritis. 325 89

It has been suggested that autoimmunity to the proteoglycan (PG) component of cartilage plays a major role in the etiology of adjuvant arthritis (AA), which occurs in rats, but not in mice, after injection of CFA. In order to more directly investigate this role, bovine and human cartilage PG were used to modulate AA, and immunity to PG was assessed. Immunization of rats or mice with PG by itself does not induce arthritis. However, in rats, a single i.v. injection of soluble PG, given 1 wk before injection of CFA, results in a significant increase in incidence and severity of the arthritis induced. Rats injected with CFA have both antibody and delayed type hypersensitivity (DTH) to PG. Upon pretreatment of rats with PG i.v., both DTH and antibody titers to PG are increased. Rats immunized with PG in IFA have high titers of anti-PG and strong DTH to PG, which are also enhanced by pretreatment with PG i.v., although none of these animals develops arthritis. In contrast to these findings in rats, when mice are pretreated with PG i.v., DTH to PG induced by injection of CFA is lower, whereas anti-PG titers are higher than in unpretreated controls. The results presented here show that, in rats, i.v. injection of PG synergizes with CFA in the induction of AA, and enhances both humoral and cellular immunity to PG. The findings support the hypothesis that immunity to PG is of importance in AA, although under the conditions of these experiments immunity induced by PG alone is clearly not sufficient for the induction of arthritis.
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PMID:The role of immunity to cartilage proteoglycan in adjuvant arthritis. Intravenous injection of bovine proteoglycan enhances adjuvant arthritis. 326 Sep 20

Sensitization of DBA-1 mice with Type II collagen (CII) in complete Freund's adjuvant can cause polyarthritis. A possible link between CII-induced arthritis and delayed type hypersensitivity (DTH) has been suggested, so we decided to investigate the susceptibility of DBA-1 mice to CII induced DTH reactions. The mice were primed with a dose of 10 micrograms CII i.p. 4 days before challenging with 40 micrograms CII in the ear. Swelling was measured 48 h later and was found to be reproducible. Responsiveness to CII could be transferred with whole spleen cell populations from primed animals or with enriched spleen T cells, thus confirming the cellular nature of the reaction. Lymph node cells from CII/CFA footpad immunized animals were restimulated with CII in vitro. These cells were able to passively transfer DTH sensitivity in vivo and exhibited specificity for this antigen in vitro in proliferation assays.
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PMID:Delayed type hypersensitivity (DTH) to type II collagen (CII) in DBA-1 mice. 349 9

Collagen-induced polyarthritis in rats is a new experimental model that shares clinical and histologic features with adjuvant arthritis. To determine whether collagen-induced arthritis is a form of adjuvant disease and to further exclude contamination of collagen with an adjuvant substance, native type II collagen was studied for adjuvant properties. IgM and IgG PFC activity and PBMC [3H]TdR incorporation were studied in rats after injection with TNP-OA combined with IFA, IFA and CII, or CFA. In general, humoral and CMI responses to TNP-OA were lower in rats injected with IFA/CII compared with those with IFA; the presence of CII during primary immunization failed to significantly enhance PFC activity to TNP after a boost. CFA-injected rats gave maximal values in both studies. Mice pretreated with BII in the absence of oil gave PFC responses below control after sensitization with SRC. Furthermore, CII was unable to replace mycobacteria in the induction of EAE in rats and was devoid of mitogenic or polyclonal stimulatory properties. It is concluded that collagen-induced arthritis is a distinct entity from adjuvant arthritis and is dependent upon the unique immunogenicity of type II collagen in rats rather than upon an adjuvant effect.
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PMID:Collagen-induced polyarthritis in rats: a study of native type II collagen for adjuvant activity. 698 10

An acute inflammatory arthritis has been induced in 76% of rats injected intradermally with native bovine type II collagen emulsified in Freund's complete (CFA) or incomplete (ICFA) adjuvant. The arthritis became chronic in 14 out of 31 rats, and ear and tail lesions were noted in some rats. No arthritis was induced by native type I collagen, denatured type II collagen, rabbit IgG, or buffer alone injected intradermally with adjuvant. Using a solid-phase radioimmunoassay for serum antibodies we have shown that IgM and IgG levels to native bovine type II collagen were significantly higher in arthritic than nonarthritic rats. Antiglobulin antibody levels were not raised in arthritic rats. Equivalent antibody levels to native type II collgen were obtained whether this antigen was emulsified in ICFA or CFA. However, native type I collagen produced high antibody levels only when emulsified in CFA, indicating a difference in the immunogenicity of these collagens. These studies suggest that native type II collagen possesses arthritogenic properties in the rat and that humoral immunity may play a role in the induction of this arthritis.
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PMID:Native type II collagen-induced arthritis in the rat. I. Incidence and humoral response to collagen. 741 20

Rat adjuvant arthritis (AA) is an animal model of rheumatoid arthritis in which pannus formation and destruction of joints occur after immunization with complete Freund's adjuvant. Neovascularization is present within the synovium and may be critical for pannus growth. In this study the effects of a novel angiogenesis inhibitor, AGM-1470, on AA were evaluated. Lewis rats were immunized with CFA to induce arthritis. AGM-1470 treatment was initiated prior to arthritis onset (preventative protocol) or administered to rats with established disease (suppressive protocol). The severity of synovitis and the immunologic status of all rats were then evaluated. Using clinical and radiographic criteria, AGM-1470 significantly reduced arthritis incidence (preventative protocol) (P < 0.01) and disease severity (both protocols, P < 0.001, compared to controls) without affecting T cell function in vitro or phenotype in vivo. Additionally, histologic sections from control rats revealed marked pannus formation, destruction of bone/cartilage, and neovascularization. These findings were absent in AGM-1470-treated rats. AGM-1470 may offer a new treatment option for rheumatoid arthritis and other angiogenesis-dependent diseases.
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PMID:A novel angiogenesis inhibitor suppresses rat adjuvant arthritis. 753 34


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