Pro- and anti-inflammatory properties of human recombinant IL-1β during experimental arthritis in rats: 2. period-dependent effect (original) (raw)
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Role of interleukin 1 in antigen-induced exacerbations of murine arthritis
PubMed, 1995
The mechanism underlying the chronic and intermittent course of rheumatoid arthritis is not elucidated. In the present study, the role of interleukin 1 (IL-1) was investigated in exacerbations of antigen-induced arthritis in mice. A flare-up of smoldering inflammation (weeks 3 to 4 of antigen-induced arthritis) was inducible by injection of a small amount of methylated bovine serum albumin into the hypersensitive knee joint. Immunohistochemistry showed IL-1 expression in the synovial lining layer and in focal areas of the inflamed synovium during the flare-up. IL-1 was also measured in 1-hour culture supernatant of synovial tissue taken during the flare-up by a bioassay. The expression of both immunoreactive and bioactive IL-1 in the hypersensitive joint peaked around 6 hours after antigen (2 micrograms of methylated bovine serum albumin) injection and declined thereafter. Antigen rechallenge induced an acute joint swelling of the arthritic joint but not in the naive joint of the sensitized mouse, yet synovia of both joints produced IL-1 after antigen injection. Remarkably, a single intravenous injection of rabbit anti-IL-1 alpha and -beta antibodies 1 hour before antigen rechallenge neutralized IL-1 in the joint. Anti-IL-1 treatment significantly reduced the antigen-induced joint swelling (30 to 40%) but did not affect the profound influx of polymorphonuclear cells in the onset of the exacerbation. However, a profound relief of the inflammation (synovitis) was obtained by IL-1 blockade on day 4 of the exacerbation. Chondrocyte proteoglycan synthesis was markedly suppressed in the antigen-challenged naive knee joints suggesting that this was a direct IL-1 effect as the inflammation was insignificant. Anti-IL-1 treatment was able to maintain chondrocyte proteoglycan synthesis in the antigen-rechallenged joint, which was highly suppressed in the control group. Furthermore, the enhanced proteoglycan breakdown in the antigen-rechallenged joints was significantly decreased in the anti-IL-1 group. We concluded that IL-1 is an important mediator in exacerbations of murine arthritis, and amelioration of cartilage pathology was obtained with anti-IL-1 antibody treatment.
Arthritis & Rheumatism, 2004
Methods. PGIA and CIA were generated using standard immunization protocols with cartilage proteoglycan aggrecan (PG) or human type II collagen (CII) emulsified with Freund's complete adjuvant (CFA), and compared with PGIA and CIA generated using immunization protocols in which the same antigens were used in combination with the adjuvant DDA. Immune responses to immunizing and self PGs and CII, and the incidence, severity, and onset of arthritis were monitored throughout the experiments. In addition, a new, inexpensive, and powerful method of inducing arthritis using crude cartilage extracts is described.
Modern Rheumatology, 2005
The G-1 column (Adacolumn), a novel extracorporeal adsorption device, is now available for the treatment of such chronic inflammatory diseases as ulcerative colitis and rheumatoid arthritis. G-1 column treatment sometimes results in a rapid decrease in clinical inflammatory parameters and/or has a delayed beneficial effect on disease activity. In order to identify the scientific basis for such clinical benefits, we studied rats with adjuvant arthritis induced by immunization with Mycobacterium butyricum antigen. The potential role of G-1 column treatment on the migratory properties and immunoreactivities of leukocytes was investigated. Treatment of arthritic rats for 60 min with an extracorporeal perfusion through the G-1 column led to the adsorption of a small proportion (20%) of circulating granulocytes and monocytes. However, after G-1 treatment, the migration of radiolabeled blood granulocytes and monocytes to sites of acute dermal inflammatory reactions decreased significantly, in the case of granulocytes, almost by half. The migration of granulocytes to the inflamed hindpaws of severely affected animals was diminished in the G-1 treated group. Granulocytes that have passed through the G-1 column may stay in the bloodstream because of their markedly diminished number of adhesion molecules. A slightly increased accumulation in the liver and a decreased localization in the lung was also observed. These results may be relevant to the rapid clinical antiinflammatory effect observed in rheumatoid arthritis and
Rheumatology, 1999
Objectives. To investigate the effects of soluble interleukin-1 (IL-1) type II receptor (sIL-1RII) on a number of clinical, biochemical and histological parameters in rabbit antigeninduced arthritis. Methods. Arthritis was induced by intra-articular injection of methylated bovine serum albumin (mBSA) into rabbits pre-sensitized to the same antigen. An initial i.v. bolus of sIL-1RII was administered, followed by s.c. mini-pump dosing for 14 days, starting at the time of the arthritis induction. Animals received vehicle (saline 500 ml + 5 ml/h), low-dose sIL-1RII (13.4 mg + 1.34 mg/h) or high-dose sIL-1RII (40.2 mg + 4.02 mg/h). Results. Marked, dose-related inhibition of joint diameter, plasma prostaglandin E 2 (PGE 2), and synovial fluid IL-1a and IL-1b concentrations were seen after administration of sIL-1RII. However, synovial fluid PGE 2 concentrations and synovial fluid cell counts were not affected. A significant inhibitory effect was also seen histologically on soft-tissue swelling and joint damage with high-dose sIL-1RII. Conclusions. These results demonstrate that IL-1 plays an important role in the pathogenesis of rabbit antigen-induced arthritis, thus confirming it as an excellent animal model with respect to evaluating anti-cytokine therapies for rheumatoid arthritis.
Flare-up of experimental arthritis in mice with murine recombinant IL-1
Clinical & Experimental Immunology, 2008
Intra-articular injections of murine recombinant IL-I (mrIL-1) during the chronic phase of antigeninduced arthritis (AIA) induced a flare-up of the smouldering inflammation. The exacerbation was characterized by acute and transient joint swelling and this coincided with the extravascular accumulation of neutrophils. IL-I injected into arthriticjoints of neutropenic mice demonstrated that joint swelling was independent of the neutrophil influx into the joint. Both phenomena were absent when IL-I was injected into a naive joint. The IL-I-induced flare-up was not T cell mediated as in the antigen-induced flare-up, and suggestive evidence is presented that IL-I sensitivity depended on the resident macrophage population. This explained why the hypersensitivity is not restricted to the immunologically mediated arthritis but reflects a more general hypersensitivity of previously injured joints, e.g. zymosan-induced arthritis and IL-I-affected joints. In addition, IL-I could also potentiate the antigen-specific flare-up of chronic AIA and prolongs the duration of the exacerbation. Our data indicate that joints bearing a chronic infiltrate are at risk from exacerbations in two ways: a T cell mediated rechallenge with antigen, and a non-specific reactivation by systemic and local IL-I generation.
Biochemical Pharmacology, 1988
Comparison has been made of the in uiuo pro-intlammatory activities or porcine natural and human recombinant LY and B interleukin 1 (IL-l) after injection into the knee joints of rabbits. Both forms of pig IL-1 and human IL-l were separately equiactive in uitro in stimulating rabbit synovial fibroblasts and articular chondrocytes to synthesize prostaglandin E2 (PGE& Injection of IL-1 into the rabbit knee joint was not associated with swelling of the joint nor with the appearance of PGE, in the synovial fluid. However, all preparations of IL-1 induced a dose-dependent increase in inflammatory leukocytes in the synovial lining and joint cavity. In addition, both the (Y and fi forms of IL-1 from both species caused loss of proteoglycan from the matrix of articular cartilage. This study demonstrates that both genetically distinct forms of IL-1 have the same range of inflammatory actions within the joint and that t%ey have-similar potencies in these respects.
Arthritis in DBA/1 Mice Induced with Passively Transferred Type II Collagen Immune Serum
Scandinavian Journal of Immunology, 1990
Arthritis was induced in DBA/1 mice by passive transfer of syngeneic anti-type II collagen (CII) scrum concentrate. After transfer ofserum containing 0.2 or 0.5 mg anti-C!l auto-antibodies the first clinical signs of arthritis appeared 48 h after injection. Severe clinical arthritis was detected 96 h after injection, immunohistochemical analyses of joints 48 h after serum injection revealed synovial foci in intercarpal and mclacarpophalangeal joints of macrophage-like cells, expressing C3bi-receptors and major hislocompatibility complex class II molecules, and infiltration of few CD4+ lymphocytes. Later (96 h afler injection), ihe inflamed synovia were dominated by C3bireceptor' polymorphonuclear cells. In contrast to conventionally induced collagen arthritis (CIA), the inflammatory infiltrates, filling joint spaces and synovial tissue, were extensively dominated by polymorphonuclear cells, whereas mat;rophage-like.. cells expressing class II molecules and a few T cells were seen only in the periphery ofthe developing pannus. The anti-CH serum induced arthritis may be used as a model for sludies of humoral mediated mechanisms operating in conventionally induced CIA as well as in rheumatoid arthrilis.