Effects of soluble interleukin-1 type II receptor on rabbit antigen-induced arthritis: clinical, biochemical and histological assessment (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.
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.
Journal of Oral Pathology & Medicine, 2002
Background: In temporomandibular joint (TMJ) arthritis, there is limited knowledge of the relationship between interleukin-1b (IL-1b) and interleukin-1 receptor antagonist (IL-1ra), as well as the source of these cytokines. We investigated the development of an antigen-induced arthritis in the rabbit TMJ immunohistochemically. Methods: Unilateral TMJ arthritis was induced in 32 adult New Zealand White rabbits. From 6 h to 12 weeks after induction of arthritis, topology of IL-1b and IL-1ra were observed. Result: The acute stage of induced arthritis lasted for one week after induction, thereafter it became chronic. In the early phase of the acute stage, infiltrating inflammatory cells, as well as synovial cells, produced IL-1b and IL-1ra. In the late phase of the acute stage, the main source of these cytokines was subsynovial fibroblasts. In this phase of arthritis, IL-1b and IL-1ra did not appear to be produced by synovial cells. From the early to intermediate phase of the chronic stage, proliferating synovial cells produced IL-1b and IL-1ra. In this phase of the arthritis, these cytokines were also observed in a cluster formation in chondrocytes.
Life Sciences, 1993
The systemic effects of human recombinant Interlcukin-1g (HrlL-IB) on hindpaw edema were detclTnined in arthitis induced by human native type II collagen (CII) with muramyl dipcptidc (MDP) both iniccted on day (I. Daily treatment with HrlL-IB (I).2l.tg so) prctreatment, from D-I (the day before MDP and CII were iniected) to D3 significantly delayed the secondary inflammation in the uninjected left hindpaw, whereas the same treatment from D6 to D 10 at the end of the "primary" inflammation, enhanced the volume of the left hindpaw. Treatment from D13 to D 17 did not affect the "secondary" edema in the left hindpaw. Thus, HrlLII?, administration produces pro-or anti-inflammatory effects on a developing polyarthritis depending on when treatment is sire'ted and is most effective as an anti-inflammatory molecule when started at the peak of the the inflammatory reaction, as previously described. In view of these early findings, wc have compared the effect of adding HrlL-IB along with MDP in the sensitization procedure on the time-course of Cll-induced arthritis. No adjuvant effect of l-lrlL-11. ~, was observed. ()n the contrary, HrlL-I B significantly decrea~d the signs of inflammation in the injected hindpaw during the secondary inflammation. In addition, the immune response to type II collagen was less in the group receiving HrlL-I B, maybe because of nonspccific increase of antigen clearance. ()n the other hand, the MDP sensitization procedure enhanced the incidence of ell arthritis and significantly worsened the clinical parameters in both primary and secondary inflammations.
Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models
Cytokine & Growth Factor Reviews, 2002
Expression of inflammatory cytokines is augmented in the joints of patients with rheumatoid arthritis (RA). We found that cytokine levels are also elevated in the joints of a mouse arthritis model, human T-cell leukemia virus type I (HTLV-I) transgenic (Tg) mouse. Depletion of IL-1 by gene targeting greatly reduced the incidence of the disease, indicating the importance of this cytokine in the development of arthritis. Furthermore, IL-1 receptor antagonist (IL-1Ra)-deficient mice develop autoimmunity and arthritis spontaneously. These observations suggest that excess IL-1 signaling the causes autoimmunity. We show that IL-1 activates the immune system non-specifically by inducing CD40L and OX40 co-signaling molecules on T cells. In this review, the roles of IL-1 in the development of autoimmunity and arthritis in mouse models will be discussed.
Clinical and experimental immunology, 1989
Intra-articular injection of highly purified or recombinant interleukin 1 (IL-1) into the rabbit knee induces a transient synovitis with leucocytic infiltration into the synovial lining and joint cavity and loss of proteoglycan from articular cartilage. Tumour necrosis factor alpha (TNF-alpha), which has many of the actions of IL-1, in the dose range 50-5,000 ng induced infiltration of leucocytes into the joint but failed to cause significant proteoglycan loss from cartilage. The nature of the leucocytic infiltrate induced by intra-articular TNF-alpha was predominantly monocytic compared with the mixed polymorphonuclear (PMN)/monocytic infiltrate induced by IL-1. Neither cytokine induced the accumulation of significant numbers of lymphocytes. In addition, on a molar basis, TNF-alpha was significantly less active than IL-1 in causing cell accumulation in the joint. Injection of submaximal doses of IL-1 and TNF into the rabbit resulted in a marked synergy with respect to the accumulat...
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.