Severity Of Adjuvant Arthritis Research Articles

Ethanolic Extracts of leaves of Alstonia scholaris Linn. Modulates Chronic Inflammatory Immune Response in FCA Induced Arthritis

AIM- The aim of the present investigation is scientifically establishing the anti-arthritic activity of selected medicinal plant so that we are able to come up with a more effective and potent bioactive phytoconstituents with less side effects in comparison with existing synthetic drugs. MATERIAL & METHODS- The leaves of Alstonia scholaris were collected from campus of College of Pharmacy. All the plant materials were taxonomically identified by Dr. Gyanendra Tiwari, Senior Scientist, KNK College of Horticulture. All the plant materials were dried under shade and subjected to coarse powder for extraction process. Accurately weighed quantity of leaf powder of Alstonia scholaris were extracted using 95 % ethanol by soxhlet apparatus for 72 h. The ethanolic extracts were dried under the reduced pressure to get crude ethanolic extracts. The Wistar albino rats were divided into 10 groups of six animals in each. For the induction of chronic inflammatory response, FCA (0.1 ml) was injected through intra-articular injection in left ankle joint of rats on 0 day. The severity of adjuvant arthritis was quantified by measuring the volume of the hind paw using Plethysmograph. Body weight was measured of all groups at zero days before immunization and at 21st day after treatments over by using a single pan weighing balance. RESULTS- The preliminary phytochemical analysis revealed that different active constituent present in different extracts such as carbohydrates, proteins, amino acids, fat, oils, steroids, terpenoids, glycosides, alkaloids, tannins and other phenolics compounds. The assessment made on the 21st day showed that the A. scholaris treatments at both doses (low and high) had moderately significant and highly significant effect and reduced (p< 0.01& p<0.001) the adjuvant-induced lesions in the respective treatment groups as compared with the arthritis control group. However, standard, A. scholaris had highly significant effects (p<0.001) in recovery of RBCs and haemoglobin. They also showed highly significant effects on decrease in WBCs and ESR treated groups, also showed moderately significant effects as compared to arthritic group. CONCLUSION- Besides from the obvious therapeutic importance, these components would be useful in understanding the mechanism of diseases with higher levels of cellular and molecular level. These components could serve as lead molecules for development of prospective anti-arthritic agents. Keywords: Anti-arthritic agent, Lead molecules, Alstonia scholaris, Shronic inflammatory response, Synthetic drugs, Plethysmograph

Effects of FR167653, a dual inhibitor of interleukin-1 and tumor necrosis factor, on adjuvant arthritis in rats

The effects of FR167653, a dual inhibitor of interleukin (IL)-1β and tumor necrosis factor (TNF)-α production, on the development of adjuvant arthritis were investigated in rats. Female Sprague–Dawleys rats weighing 130 g with adjuvant arthritis were administered FR167653 0.1, 1, 10, or 30 mg/kg, and their arthritis scores, soft tissue X-rays, and histological findings were then compared with those of a control group. Body weights were also recorded. FR167653 suppressed the severity of adjuvant arthritis in a dose-dependent manner. Administration of the drug had little effect on body weight. FR167653 might locally affect arthritic joints to prevent inflammation. However, further experiments are necessary to elucidate the underlying mechanisms.

Behavior and Severity of Adjuvant Arthritis in Four Rat Strains

Previous research has suggested that behavioral traits of the histocompatible Lewis and Fischer strains of rats could be related to the difference in their susceptibility to adjuvant arthritis (AA). In the present study, the predictive value of behavioral markers in susceptibility to AA was investigated in nonhistocompatible inbred DA, Lewis, Albino Oxford (AO), and outbred Wistar strain. Behavioral profiles (open filed test and forced swim test) were determined prior to immunization with a single intradermal injection of complete Freund's adjuvant. Animals were daily scored for clinical signs of AA. The occurrence of certain behaviors and clinical indices of AA was significantly associated with strain membership. Discriminant analysis identified strain-related behavioral and illness profiles with very few overlaps among the phenotypes. Discriminant classification significantly exceeded the proportion of cases, which could have been correctly classified on the basis of chance. Open field behavior, in particular, exploration and grooming, differentiated among AA-susceptible and AA-resistant strains. Multiple regression analysis indicated that severity of AA (maximum clinical sign) can be predicted by the latency time and grooming behavior in the open field independently of strain membership. No clear distinction between AA-susceptible and AA-resistant strains was found with respect to forced swim test immobility. It was concluded that (a) strain-related genetic predisposition is important for the expression of certain behavioral traits and for susceptibility to AA and (b) open field behaviors, particularly grooming and latency, predict susceptibility to AA across different rat strains.

Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis.

Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.

Treatment of adjuvant arthritis in rats: Vaccination potential of a synthetic nonapeptide from the 65 kDa heat shock protein of mycobacteria

Adjuvant arthritis induced by mycobacteria in rats is a widely used model of chronic arthritis. A previously described nonapeptide (Thr-Phe-Gly-Leu-Gln-Leu-Glu-Leu-Thr, amino acid sequence 180–188) from the recombinant 65 kDa heat shock protein of Mycobacterium bovis BCG, which was found to contain a T-cell epitope recognized by both arthritogenic and protective T-cell clones in vitro, has been investigated for its vaccination and therapeutic potential in adjuvant arthritis in rats. The nonapeptide was found not to be arthritogenic, although the T cells from nonapeptide immunized rats cross-react in vitro with mycobacterial antigens. Intraperitoneal administration of 0.1 mg nonapeptide in oil at day −20 or days −2, −1 and 0, resulted in a marked reduction of incidence and severity of adjuvant arthritis. The disease process and severity were also influenced by therapeutic treatment with 0.1 mg nonapeptide injected intraperitoneally at days 7 to 10. Interestingly, subplantar or intravenous application of the nonapeptide had no influence on the disease process. Deletion of the N-terminal threonine led to complete loss of in vivo activity of the nonapeptide.

Suppression of collagen arthritis in rats by heterologous anti-idiotypic antisera against anticollagen antibodies

Affinity-purified rat anti-type II collagen antibodies were used to prepare anti-idiotypic antibodies in rabbits. It has been demonstrated that such anti-idiotypic antibodies are capable of binding to anti-type II collagen antibodies in vitro. Intravenous administration of heterologous anti-idiotypic antisera at the time of immunization with type II collagen resulted in a significant suppression of anti-type II collagen antibody formation and the development of arthritis, although delayed-type hypersensitivity skin test response to type II collagen was not affected. However, treatment of rats with heterologous anti-idiotypic antisera at Day 7 after immunization was ineffective in altering disease expression. On the other hand, treatment with heterologous anti-idiotypic antisera had no significant suppressive effect on the incidence or severity of adjuvant arthritis. These results indicate that the effect of heterologous anti-idiotypic antisera directed toward anti-type II collagen antibodies is disease specific and is restricted to collagen arthritis.

Influence of tubercle aggregate size on severity of adjuvant arthritis in the rat.

Incorporation into Freund's complete adjuvant of tuberculous aggregates smaller than 90 mum in size is essential to produce adjuvant arthritis in the rat, and this correlates with a significantly greater degree of cell-mediated immunity to tuberculous antigens produced by small aggregates (smaller than 90 mum), when compared with large (larger than 90 mum) aggregates. This requirement for small aggregates to render Freund's complete adjuvant arthritogenic is not paralleled by detectable differences in antimycobacterial humoral antibody production nor by a size-dependent requirement for a conventional adjuvant effect.

Proceedings: Influence of tubercle aggregate size on the severity of adjuvant arthritis in the rat.

Proceedings: Influence of tubercle aggregate size on the severity of adjuvant arthritis in the rat.

Effect of infection with trypanosomes on the development of experimental allergic neuritis in rabbits.

DATA obtained from hospitals in western Nigeria1 have shown that rheumatoid arthritis is uncommon in that region and, when the disease occurs, it is clinically milder than in Europeans, involving few of the expected immunological changes2,3. Other conditions in which auto-immune processes are thought to be involved were also found to be rare, and Greenwood suggested that repeated exposure to parasitic infections might be responsible, at least in part, for the infrequent occurrence of these auto-immune diseases. Infection with the rodent malaria parasite Plasmodium berghei yoelii delayed the onset of haemolytic disease in 4 week old NZB mice and prevented the development of renal disease in (NZB×NZW) F1 mice at the same age4. The severity of adjuvant arthritis in rats was also reduced by simultaneous inoculation of P. berghei yoelii, which produces a very mild infection, but not by infection with a more virulent strain of P. berghei berghei5. We are investigating the effects of trypanosome parasites on the development in rabbits of experimental allergic neuritis (EAN), a demyelinating paralytic disease6, the genesis of which is primarily a cell-mediated type of immune response (manuscript in preparation), and the preliminary results are reported here.

Differences in the severity of adjuvant arthritis in four strains of rats.

SummaryThe development of adjuvant-induced arthritis was studied in four strains of rats. Using injected and noninjected hind foot volumes and a secondary lesion scoring system as parameters of the disease, Holtzman rats were adjudged to develop the most and Buffalo rats the least severe arthritis of the four strains.