Course Of Adjuvant Arthritis Research Articles

Die pustulöse Arthro-Osteitis - Modell einer reaktiven Spondarthritis?

Pustulotic arthro-osteitis exemplifies the fact that the catalogue of nosological entities is by no means complete even in rheumatology and that individual symptoms are being recorded by various authors of different disciplines at different times, independent of each other, resulting in a jig-saw puzzle of individual observations that may take years to fit together. As far as pustulotic arthro-osteitis is concerned, it is a particularly unusual and fascinating fact that this disease appears to be a combination of palmo-plantar pustulosis, sternoclavicular hyperostosis and a variety of other skeletal changes plus tangential connections to other (related?) diseases. There are some pointers indicating that it is a reactive spondylarthropathy that is identical with chronic multifocal osteomyelitis occurring in childhood and adolescence. It is interesting to note that very similar arthritic changes have been seen in the course of adjuvant arthritis in the rat where T-lymphocytes were employed. In this particular phenomenon in the rat an abacterial (in this case probably immunologically mediated by the T-lymphocytes) chronic hyperostotic osteomyelitis may also occur.

Time Course of Antibodies against IgG and Type II Collagen in Adjuvant Arthritis. Role of Mycobacteria Administration in Antibody Production

The aim of this study was to elucidate, during the time course of adjuvant arthritis, the existence of antibodies directed to IgG (rheumatoid factor-like) and antibodies against type II collagen. In a second study, we also studied the relation between antibody production, arthritic process and mycobacteria administration. We have demonstrated the presence of antibodies to IgG and type II collagen by means of ELISA techniques. This reactivity appeared on day 7 post-induction, decreased later, and increased progressively from day 21 until last day studied (day 56 post-induction). We have also quantified antibodies against a soluble fraction of Mycobacterium butyricum, the inductor of the disease. Anti-mycobacteria antibodies appeared during the first seven days after induction, but from day 14, when systemic inflammation began, their levels suddenly increased. There is a positive correlation between anti-mycobacteria antibody levels and articular swelling. Anti-IgG and anti-collagen antibody production was not directly linked to arthritic process since these antibodies were synthesized when M. butyricum was administered intraperitoneally, which does not induce arthritis. Anti-mycobacteria antibody concentration was higher when arthritis induction by mycobacterial was successful than when it was unsuccessful.

Anti-Type I Collagen Antibodies in Advanced Phases of Adjuvant Arthritis

The aim of this study was to elucidate the existence of autoantibodies directed to type I collagen as a response to connective tissue alterations that occur in inflammatory diseases. We have demonstrated the presence of antibodies to type I collagen during the time course of adjuvant arthritis, by means of the ELISA technique. These autoantibodies reached the highest levels in advanced phases of the arthritic process from 8 to 10 weeks after mycobacteria administration. The hind-paw swelling and the anti-type I collagen antibodies remained for at least 18 weeks post-induction.

Interleukin-6 (IL-6) in adjuvant arthritis of rats and its pharmacological modulation

The levels of serum interleukin-6 (IL-6) were measured during the course of adjuvant arthritis (FAA) in male Lewis rats. In the course of the disease serum IL-6 levels increase with a clear correlation with morphologic disease signs. Additionally, the FAA-inducing antigen, heat-killed Mycobacterium tuberculosis, was found to be a strong inducer of IL-6 production by spleen cells in vitro. The effects of the anti-rheumatic drugs indometacin, dexamethasone, cyclophosphamide and cyclosporin A (CsA) on IL-6 levels during FAA were determined. Complete normalization of serum IL-6 levels was observed with dexamethasone, cyclophosphamide and CsA whereas indometacin only partly reduced serum IL-6 levels.

Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein.

The mycobacterial 65 kDa heat shock protein (HSP65) is of critical significance in the model of adjuvant arthritis (AA). Arthritogenic and protective T cell clones obtained from arthritic rats recognized the 180-188 sequence of HSP65. Previous reports have shown that administration of HSP65 prior to disease induction led to resistance to arthritis in the AA model and in several other models of experimental arthritis. Here, we report the development of immunity to HSP65 and the critical 180-188 epitope during the course of AA. Following Mycobacterium tuberculosis (MT) immunization both antibodies and T cell responses to HSP65 were detected. Proliferative responses to the 180-188 epitope were seen exclusively in the local draining lymph node cells at day 14 after immunization. The anatomical distribution and course of T cell responses to HSP65 and its 180-188 epitope are compatible with T cell regulated control of the disease. Although lower HSP65 antibody levels were observed in the animals with severe arthritis, in individual animals no evidence was obtained for a relationship between development of HSP65 humoral immunity and arthritis severity. Nevertheless, during disease exacerbation, elicited by HSP65 immunization during disease development, elevated T cell responses against HSP65 and its 180-188 epitope were found. In contrast, we obtained evidence that successful transfer of arthritis resistance to naive recipients depends on the transfer of HSP65 specific T cells. On the basis of these results, it seems that HSP65 plays a crucial role in the T cell regulatory events involved in both the induction of, and protection against, AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the chronic phase of adjuvant arthritis: effect of SR 41319, a new diphosphonate.

We studied the course of adjuvant arthritis in rats by measuring clinical, biochemical, and histological parameters on day 36 after induction (representing the secondary reaction) and on day 171, which is at the stage of permanent deformity. The effect of SR 41319, a new diphosphonate, was evaluated on days 36 and 171, after three weeks of treatment (days 14-35 inclusive). In the absence of treatment all the measured parameters were markedly abnormal on day 36, indicating the presence of lesions that were still evolving. On day 171 clinical parameters and the lesion histological index remained the same, whereas the biochemical parameters and disease activity histological index had returned to normal, indicating that the lesions at this stage although severe were not inflammatory and consequently not progressing. SR 41319 treatment reduced the severity and progression of the disease both on day 36 and on day 171. We conclude that SR 41319 may be a potentially useful drug for the treatment of rheumatoid arthritis.

The effect of some antirheumatic drugs in vivo on the response of spleen cells to concanavalin A in rats with chronic inflammation

During the course of adjuvant arthritis in rats adherent spleen cells inhibited the response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con A). The effects of 14 days treatment with various antirheumatic drugs on spleen cell responsiveness to Con A were investigated. Two nonsteroidal anti-inflammatory drugs, indomethacin (1 mg/kg/day p.o.) and acetylsalicylic acid (200 mg/kg/day p.o.) did not modify the spleen cell response, whereas treatment with chloroquine (50 mg/kg/day p.o.) or levamisole (5 mg/kg/day p.o.) further increased the inhibitory effects of the adherent suppressive spleen cells. On the contrary, treatment with sodium aurothiomalate (10 mg/kg/day i.m.), D-penicillamine (50 mg/kg/day p.o.) or pyritinol (50 mg/kg/day p.o.) significantly enhanced the response of th e lymphocytes to Con A. In addition to the effects on spleen cell responsiveness, the ability of the various drug treatments to modify the polyarthritic lesions of the disease was investigated. It is suggested that this model may provide a valuable approach for evaluating the effects of antirheumatic drugs in vivo on immunological responsiveness during chronic inflammatory disease.

Autoimmunity to collagen in adjuvant arthritis of rats.

Arthritis can be induced in rats by intradermal injection of oil containing bacterial derivatives (adjuvant-induced arthritis) or cartilage collagen (type II collagen-induced arthritis). It was of interest, therefore, to determine whether collagen functions as an autoantigen in rats with adjuvant arthritis. Blood mononuclear cells from the majority of rats with adjuvant arthritis exhibited enhanced thymidine incorporation to homologous types I and II collagens, as well as to purified protein derivative of tuberculin. In contrast, cells from rats remaining nonarthritic after injection of adjuvant did not respond to collagen, although they did react to tuberculin. Similar results were obtained with a radiometric ear assay used to quantify intradermal delayed-type hypersensitivity in vivo. Using passive hemagglutination, autoantibodies to these collagens and their denatured alpha-chains were frequently detected in the sera of rats late in the course of adjuvant arthritis. Rats with inflammation of a hindlimb induced by turpentine did not acquire sensitivity to collagen. These data indicate that autoimmunity to collagen is a common feature of adjuvant- and collagen-induced arthritis, both of which are considered to be mediated by immunologic mechanisms.

Sex-related differences in the impairment of hepatic drug-metabolizing enzymes in rats with adjuvant disease

1.1. We have studied the optimum conditions for the induction of adjuvant carrageenan-induced inflammation (ACII) in male Wistar rats with limited susceptibility to adjuvant arthritis (AA).2.2. ACII was induced by intradermal injection of Freund's complete adjuvant (CFA), containing 10 mg/ml Mycobacterium tuberculosis, followed by a subplantar inoculation of the nonspecific inflammatory stimulus carrageenan at different times.3.3. Data obtained indicate that the arthritis of rats inoculated with CFA is significantly increased by carrageenan, particularly when it is injected 14 days after the adjuvant. Arthritis enhancement was more evident in the joints of the leg that had been previously injected with carrageenan, and remained stable around the peak level for some weeks. The development of joint inflammation was associated histologically with the appearance of inflammatory cells in the synovial membrane of those animals.4.4. We found that the injection of carrageenan aggravated the course of AA in general, but very significantly when administered at the moment of the appearance of arthritis (day + 14). This aggravation affected both the intensity of inflammation and the chronicity of the disease.

Genetische Unterschiede in der Augenmanifestation der Adjuvansarthritis der Ratte

The results of crossbreeding experiments between several strains of rats are reported. They show differences in the prevalence of iritis in the course of adjuvant disease as did the results we published in an earlier article. There are alterations which indicate a recessive heredity of the tendency to iritis. The contribution of genetic factors in the course of adjuvant arthritis has been confirmed by the present results.

Effect of prostaglandin E2 on adjuvant arthritis.

THE prostaglandins are a class of cyclic, unsaturated, oxygenated fatty acids1,2 and their effects on capillary permeability3, corticosteroidogenesis4 and peripheral circulation5, as well as the prostaglandin-like activity found in inflammatory exudate6, suggested to us a possible therapeutic use in inflammatory conditions. We have studied the effects of prostaglandin E2 (PGE2) on the development and course of adjuvant arthritis in rats. Adjuvant arthritis7 is a laboratory model for chronic joint inflammation, and the lesions produced resemble those seen in clinical rheumatoid arthritis7,8. PGE2 proved effective in both prophylactic and therapeutic regimens.

Sparing effect of neurological deficit and trauma on the course of adjuvant arthritis in the rat.

<h3>Abstract</h3> The maternal brain displays considerable plasticity, and motherhood is associated with changes in affective and cognitive function. Motherhood can alter the trajectory of brain ageing, including modifications to neuroplasticity and cognition. Here, we investigated the short- and long-term effects of motherhood on hippocampal neurogenesis, microglial density and morphology, and circulating cytokines, domains known to be altered with age and implicated in cognition and mood. Female rats were bred then euthanized during gestation or at various postpartum timepoints, culminating in middle age, and nulliparous rats served as age-matched controls. Hippocampal neurogenesis was significantly suppressed during gestation and the postpartum period. Interestingly, neurogenesis declined significantly in middle-aged nulliparous rats, but increased in primiparous rats across the same period. Transient postpartum adaptations to the neuroimmune environment of the hippocampus were evidenced, as Iba-1-immunoreactive microglia assumed a de-ramified morphology followed by increased density. Intriguingly, ageing-related changes in circulating cytokines were dependent on parity. These adaptations in neurogenic and immune processes may have ramifications for maternal mood and cognition across the peripartum period and beyond.