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)

The effects of treatment with a monoclonal antibody (R73 mAb) against T cell receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA) and established collagen-induced arthritis (ECIA) in rats have been investigated. Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and minimal erosion of cartilage, whereas arthritic rats treated with PBS and an irrelevant control mAb against Giardia had marked hyperplasia of synovium with pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced formation of pannus containing many inflammatory cells and marked cartilage and subchondral damage similar to those in arthritic rats that received the control treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb treatment was associated with marked reduction in arthritogen-specific delayed-type hypersensitivity responses in both EAA and ECIA. The titers of antibodies against type II collagen produced in rats with ECIA were not affected by the mAb. Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in chronic ECIA.
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PMID:Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats. 137 48

In this report we are able to show that intravenous (i.v.) application (day 0) of a nonapeptide (residues 26-34) from the human C1q A-chain (designated peptide A-C1q) prior to intradermal (i.d.) administration of chicken type II collagen (CII) in arthritis-susceptible DBA/1 mice (H2q), leads to abrogation of polymorphonuclear neutrophil (PMN) invasion into the joints. This nonapeptide exhibits epitope characteristics and high homology to residues 137-147 of CB11 (a cyanogen bromide fragment of chicken CII, known to contain both arthritis inducing and suppressing determinants). Arthritis index was lowest in animals pretreated i.v. with CII (as internal control), though animals pretreated i.v. with peptide K (residues 137-147 with an additional glycine residue from CB11) or peptide A-C1q exhibited comparative arthritic indices. Only in the arthritis-positive control group (day 0: PBS i.v.) did i.d. application of CII lead to invasion of PMN into the synovial layer and the joint space. Analysis of antibody (Ab) responses at day 48 after i.v. immunization (day 0) and CII challenge (day 7) revealed IgE-Abs to native CII and also to native C1q. IgG titers to CII were highest in animals pretreated with peptide A-C1q. Abs from this group, exhibiting activity to peptide A-C1q (immunizing antigen), were of mainly IgG1 and IgG3 isotypes. Evaluation of the immune response following i.v. application of peptide A-C1q or CII, prior to i.d. CII administration, in DBA/1 mice, revealed IgM responses to peptide A-C1q and peptide K, but not to CII. Intravenous application of peptide A-C1q led to generation of IgG3-Abs reacting only with peptide A-C1q and peptide K, but not with native CII. Additionally, i.v. application of peptide A-C1q elicited IgG responses to a pentapeptide, resembling amino acid residues 26-30 (K-G-E-Q-G) of the C1q A-chain. This five residue antigenic determinant is present in peptide K, in chicken and human CII as well as in human C1q. No specific IgE response to any of the antigens tested could be detected. Since a peptide from the C1q A-chain is both capable of eliciting immune responses and modulating CII-induced arthritis in mice, we postulate that the collagen-like complement component C1q is involved in the development of CII-induced inflammatory arthritic lesions, and may represent, in vivo, the early antigen responsible for inducing anticollagen antibodies prior to CII in hyaline cartilage becoming available as antigen.
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PMID:Modulation of type II collagen-induced arthritis in DBA/1 mice by intravenous application of a peptide from the C1q-A chain. 139 37

In an attempt to examine the in vivo proinflammatory properties of IL-1, the effects of rIL-1 beta on the development of collagen-induced arthritis in mice were investigated. The results presented in this paper demonstrated that the administration of rIL-1 beta via mini-osmotic pumps into DBA/1 mice which were suboptimally immunized with native chick type II collagen (NcII) markedly accelerated the onset as well as the progression of the arthritic disease. When IL-1-containing osmotic pumps were s.c. implanted onto mice 18 days post-collagen immunization, clinical signs of arthritis appeared within 3 to 4 days after the implant with the pumps. Maximal incidence of arthritis which was usually 80 to 100% occurred between the 6th and 7th day after the administration of rIL-1 beta. Histologic analyses revealed that the knee and ankle joints from mice which were treated with rIL-1 beta for 7 days were most severely and consistently affected. Furthermore, these IL-1-treated mice exhibited granulocytic hyperplasia within the marrow as well as marked peripheral blood neutrophilia. By contrast, arthritis was not observed during the 7-day course of the IL-1 study in the following control groups: 1) mice that were only immunized with NcII, and 2) collagen-immunized mice which received osmotic pumps containing PBS. A substantial number of these collagen-immunized mice which were not treated with IL-1 eventually developed arthritis but at later times after the incidence of arthritis had peaked in the IL-1-treated group. In addition, unimmunized mice failed to develop arthritis upon treatments with IL-1 beta. Moreover, the humoral responses to NcII were not altered in the IL-1-treated mice. Thus, these in vivo studies suggest that IL-1 is potentially capable of triggering the various inflammatory events of collagen-induced arthritis, and thereby, contribute to the pathogenesis of murine arthritis.
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PMID:In vivo administration with IL-1 accelerates the development of collagen-induced arthritis in mice. 326 Sep 13

The present paper summarizes the experience of the authors in the setting up of the radioimmunoassay (RIA) for human follicle simulating hormone (H-FSH), with the purified antigen for radioiodination, the F-FSH standard and the specific antibodies kindly donated by the National Pituitary Agency of the National Institutes for Arthritis, Metabolic and Digestive Diseases of the National Institutes of Health, Bethesda, MD. U.S.A. The conditions for the RIA have modified somewhat and simplified with respect to the suggested instructions accompanying the reagents. Thus, the amount of Chloramine T and the time of exposure of the labeled H-FSH (H-FSH) has been studied. It is always purified on Sephadex G-100 immediately before addition to the RIA and in this manner it may be used for up to 2 month after labeling when kept at --20 degrees C. Curves obtained at different dilutions of the H-FSH Standard, carried out with phosphosaline buffer, pH 7.4-7.8 (PBS) containing 1 % human serum albumin, or with horse plasma, of with PBS containing 0,25 % serum from non-immune rabbits (RIA Buffer) have been compared iwth those abtained by serial dilutions of sera from post-menopausal with these diluents. The most consistent results were obtained with the RIA buffer as diluent. The redisual error was smaller, and serial of dilution curves of the H-FSH standard were parallel to those of plasma and acetone precipitates of urine from post-menopausal women. Parallelism was not god using those serum. Results using PBS contianing human seum albumin were poor. PBS containing bovine serum albumin was avoided as some batches were found to interfere with the binding of the F-FSH to the antibody. The stability of the different dilutions of the H-FSH standard prepared in RIA buffer was tested. It was found that the standard curves could be prepared, pipetted into the RIA tubes and kept ready, frozen at --20 degrees C for one to two months. This shortens the actual setting up of a given RIA and decreases interassay variation of results. Parallelism of the H-FSH standard curve with serial dilutions (in RIA-buffer) of sera from women on the day of the preovulatory was confirmed. The data obtained in men and women, during stimulation with LH-RH are also given. No cross reactivity was found the HCG or sera from women, in agreement with the fact that the antiserum had been absorbed with HCG. There is, however, a considerable degree of cross reactivity with H-TSH; Thus, sera containing 15 muU/ml H-TSH or more, would give false H-FSH results. Such H-TSH values are not only found in hypothyroid patients, but might be reached during TRH responses to TRH.
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PMID:[Validation of the radioimmunoassays for pituitary gonadotropins II. Human follicle stimulating hormone (author's transl)]. 446 72

Collagen-induced arthritis (CIA) developed in 70 to 90% of rats immunized with heterologous type II collagen. CIA was reduced to 0 to 18% when rats were injected i.v., i.e., pretreated, with 1 mg of soluble native type II collagen before immunization. Concomitant with the suppression of CIA were significant suppression of IgM, IgG, and delayed-type hypersensitivity (DTH) responses to type II collagen. Suppression of CIA and immunity to collagen was antigen-specific, related to dose and route of administration, and occurred only when 1 mg of collagen was injected i.v. either 32, 7, or 4 days before, or 7 days after immunization. Once CIA was established, however, neither arthritis nor immunity could be suppressed. To determine if adjuvant-induced arthritis (AIA), like CIA, could be suppressed by i.v. pretreatment with type II collagen, rats were given 1 mg of type II collagen or PBS i.v. before injection with mycobacteria and oil. AIA was not suppressed, and arthritis appeared in both groups at a similar incidence and severity. Sera from 26 rats with severe AIA that was collected between days 14 and 35 after injection were assayed for IgG to homologous rat type II collagen and were found to be negative. These findings further support the hypothesis that CIA in rats is mediated by immunity to type II collagen and also suggest that CIA and AIA have different primary pathogenic mechanisms.
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PMID:Collagen-induced arthritis in rats: antigen-specific suppression of arthritis and immunity by intravenously injected native type II collagen. 619 9

Collagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulate the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs. These consist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B cells, a mouse IgG2b recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies of the same species class and subclass. In the case of anti-B220 antibodies, the effects of treatment were compared with administration of PBS. Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible mechanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb are discussed.
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PMID:Anti-CD5 therapy decreases severity of established disease in collagen type II-induced arthritis in DBA/1 mice. 752 41

The Dark Agouti (DA) rat has been shown recently to have a high susceptibility for developing arthritis when challenged with either heterologous or homologous collagen II mixed with mineral oil, or with mineral oil challenge alone. This study determined the arthritogenic potential of silicone gel by either mixing it with bovine collagen II (BII) or by injecting silicone gel alone in DA rats. The incidence of collagen induced arthritis was as follows: PBS group- 0/10, silicone gel group- 4/10, and IFA group- 8/9. Anti-BII antibodies were formed in most of the rats treated with either silicone gel or IFA and these groups of rats showed a positive DTH reaction. The PBS treated rats were negative for both anti-BII antibodies and DTH reaction. The incidence of arthritis formation in rats injected with silicone gel alone was 0/10, while the IFA injected rats showed an incidence of 8/10. Silicone gel taken from a commercial breast implant thus is capable of mediating collagen induced arthritis in the DA rat. However, silicone gel alone does not appear to be arthritogenic.
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PMID:Induction of type II collagen arthritis in the DA rat using silicone gel as adjuvant. 856 48

The relative safety (or otherwise) of silicone gel filled breast implants remains a controversial issue. The Dark Agouti (DA) rat has been shown recently to have a high susceptibility for developing arthritis. This study determined the arthritogenic potential of silicone gel, silicone oil, and the low molecular weight octamethylcyclotetrasiloxane (D4), by either mixing it with bovine collagen II (BII) or by injecting silicone gel alone in DA rats. Three separate experiments were performed using 110 female DA rats with 10 rats per treatment group. The incidence of collagen induced arthritis was as follows: Experiment I (6 micrograms BII)- PBS = 0/10, silicone gel = 4/10, and IFA = 8/9; Experiment II (125 micrograms BII)- PBS = 0/10, silicone gel = 7/10, IFA = 10/10, 1,000 cs silicone oil = 3/10, D4 = 0/10, and 1% D4 in 1,000 cs silicone oil = 1/10; Experiment III (adjuvant alone)-IFA = 8/10, silicone gel = 0/10. Anti-BII antibodies were formed in most of the rats treated with either silicone gel or IFA mixed with BII and these groups of rats showed a positive DTH reaction. The PBS treated rats were negative for both anti-BII antibodies and DTH reaction. Silicone gel taken from a commercial breast implant thus is capable of mediating collagen induced arthritis in the DA rat. However, silicone gel alone does not appear to be arthritogenic.
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PMID:Induction of type II collagen arthritis in the DA rat using silicone gels and oils as adjuvant. 857 29

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.
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PMID:Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity. 891 74

The long-term effects of acutely administered clodronate (free or liposome-encapsulated) on periarticular bone mass and bone turnover were investigated in chronic antigen-induced arthritis (AIA; day 28). Wistar rats were treated intraperitoneally at 3 h and on days 1, 2, and 7 of AIA, with phosphate-buffered saline (PBS; sham), PBS-containing liposomes, free clodronate, or liposome-encapsulated clodronate (cumulative dose, 3.64 mg/animal). In the primary spongiosa (</=1 mm from the growth plate) sham-treated AIA was associated with a significant decrease (-31%) of trabecular bone volume only; this change was not prevented by any treatment. In the secondary spongiosa (>1.25 mm from the growth plate), sham-treated AIA was associated with: (a) a marked significant decrease in trabecular bone volume (-56%); (b) a significant increase of osteoid-covered surface (+135%); and (c) a numerical increase of resorption surface with osteoclasts (+96%). In the secondary spongiosa, free clodronate completely prevented the loss of periarticular bone mass and selectively normalized the parameters of bone formation (i.e., osteoid-covered surface and osteoid-covered surface with osteoblasts). Clodronate liposomes, in addition to these effects, also significantly suppressed bone resorption (i.e., resorption surface covered with osteoclasts). The effects of clodronate liposomes coincided with in vivo targeting of osteoclasts in primary and secondary spongiosa. Thus, low-dose, acutely administered clodronate, both in free and encapsulated forms, exerts an excellent preventive effect on bone loss in the secondary spongiosa of chronic AIA.
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PMID:Periarticular bone alterations in chronic antigen-induced arthritis: free and liposome-encapsulated clodronate prevent loss of bone mass in the secondary spongiosa. 988 55


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