Suppression of monocyte function and differential regulation of IL 1 and IL 1ra by IL 4 contribute to resolution of … (1993 Nov)
suppression of monocyte function and differential regulation of IL 1 and IL 1ra by IL 4 contribute to resolution of experimental arthritis . IL 4 has diverse effects on hematopoietic cells , including the ability to suppress certain mononuclear cell functions . To evaluate the effect of IL 4 on the evolution of acute and chronic arthritis , murine recombinant IL 4 was administered systemically to animals receiving an arthropathic dose of group A streptococcal cell wall fragments . daily treatment with IL 4 had a minimal effect on the acute phase , but significantly suppressed the chronic , destructive phase . By 4 wk after initiation of disease , the articular index of IL 4 treated animals was reduced 60 ( articular index 4 / 0 . 9 ) compared with the untreated rats ( 11 . 5 / 0 . 48 , p 0 . 001 ) . A substantial decrease in the influx of inflammatory cells and virtual elimination of pannus and erosions occurred after IL 4 therapy . associated with the reduced accumulation of mononuclear leukocytes was a decrease in their proinflammatory functions including cytokine production and reactive oxygen intermediate metabolism . these observations are consistent with the selective effects of IL 4 on phagocytic cell function demonstrated in vitro . furthermore , IL 4 induced gene expression for IL 1ra , a protein that antagonizes the action of IL 1 by binding to the IL 1 receptor without agonist activity . through an expanding spectrum …

Gene transfer to human joints : progress toward a gene therapy of arthritis. (2005 Jun)
Gene transfer to human joints : progress toward a gene therapy of arthritis . This article describes the clinical application of gene therapy to a nonlethal disease , rheumatoid arthritis ( RA ) . intraarticular transfer of IL 1 receptor antagonist ( IL 1Ra ) cDNA reduces disease in animal models of RA . whether this procedure is safe and feasible in humans was addressed in a phase I clinical study involving nine postmenopausal women with advanced RA who required unilateral sialastic implant arthroplasty of the 2nd 5th metacarpophalangeal ( MCP ) joints . cultures of autologous synovial fibroblasts were established and divided into two . One was transduced with a retrovirus carrying IL 1Ra cDNA ; the other provided untransduced , control cells . In a dose escalation , double blinded fashion , two MCP joints were injected with transduced cells , and two MCP joints received control cells . One week later , injected joints were resected and examined for evidence of successful gene transfer and expression by using RT PCR , ex vivo production of IL 1Ra , in situ hybridization , and immunohistochemistry . All subjects tolerated the protocol well , without adverse events . unlike control joints , those receiving transduced cells gave positive RT PCR signals . synovia that were recovered from the MCP joints of intermediate and high dose subjects produced elevated amounts of IL 1Ra ( P 0 . 01 ) . clusters of cells expressing high levels of IL 1Ra were …

Anti type II collagen antibody accelerates arthritis via cxcr2 expressing cells in IL 1 receptor antagonist deficient mice. (2007 Oct)
Anti type II collagen antibody accelerates arthritis via cxcr2 expressing cells in IL 1 receptor antagonist deficient mice . arthritis can be induced in mice by the injection of anti type II collagen ( anti CII ) Ab and LPS . To elucidate the role of IL 1 receptor antagonist ( IL 1ra ) in Ab induced arthritis , WT and IL 1ra ( / ) mice were administered anti CII Ab and LPS . these IL 1ra ( / ) mice developed severe arthritis even at low doses of anti CII Ab and LPS , while WT mice did not . The cells that invaded the arthritic joints were mainly Gr 1 ( ) neutrophils , and the number of the cells in the joints remained high over 4 weeks in the IL 1ra ( / ) mice . KC , a ligand for cxcr2 , is found in higher levels in the arthritic paws of IL 1ra ( / ) mice compared with the WT , and most of the cells that infiltrated into the joints of the IL 1ra ( / ) mice were cxcr2 expressing neutrophils . administration of anti cxcr2 Ab completely inhibited arthritis development . The anti cxcr2 Ab decreased the number of neutrophils in the blood and also inhibited the migration of neutrophils to KC . these results suggested that the high susceptibility of IL 1ra ( / ) mice to anti CII Ab induced arthritis was due to the higher expression of …

Cytokines and acute phase proteins in rheumatoid arthritis. (1995 Mar)
cytokines and acute phase proteins in rheumatoid arthritis . cytokines are extracellular signalling glycoproteins that play an important pathological role in rheumatoid arthritis ( RA ) where they mediate acute inflammation , chronic inflammation and connective tissue destruction . In RA the macrophage derived cytokines such as interleukin 1 ( IL 1 ) , interleukin 6 ( IL 6 ) , interleukin 8 ( IL 8 ) , tumour necrosis factor ( TNF ) , colony stimulating factors ( CSFs ) and growth factors play a key role in amplifying and perpetuating inflammation . IL 1 and TNF activate cartilage and bone degrading enzymes , while IL 8 recruits inflammatory cells into the joint . IL 1 and TNF play an important role in the acute phase response in that they potently induce IL 6 , itself the major mediator and regulator of hepatic synthesis of acute phase proteins ( APPs ) . The acute phase response is signalled by the rapid elevation of APPs such as C reactive protein ( CRP ) and serum amyloid A ( SAA ) in the blood , and these can be used as good surrogate markers of disease activity . In health , the activity of cytokines such as IL 1 or TNF is checked by inhibitory molecules such as receptor antagonist molecules or soluble receptor molecules . In disease , cytokine activity appears to be relatively unopposed , leading to the recent development of cytokine inhibitory molecules as potential anti RA therapies …

Variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biopsies : quantification using color video image analysis. (1998 Feb)
variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biopsies : quantification using color video image analysis . objective : To investigate the variability in immunostaining for cytokines and cell adhesion molecules using multiple arthroscopically directed synovial biopsies from within a rheumatoid knee joint , quantitated by color video image analysis . methods : needle arthroscopic biopsies were taken from multiple sites ( 4 7 sites ) around a knee joint in 8 patients with rheumatoid arthritis ( RA ) . In 5 patients , immunoperoxidase staining for the cytokines tumor necrosis factor alpha ( TNF alpha ) , interleukin 8 ( IL 8 ) , and IL 1beta as well as the IL 1 receptor antagonist protein ( IL 1ra ) was performed . In 3 patients , immunoperoxidase staining for the cell adhesion molecules E selectin ( cd62e ) , P selectin ( cd62p ) , intercellular adhesion molecule 1 ( ICAM 1 , CD54 ) , and platelet endothelial cell adhesion molecule ( pecam , CD31 ) was performed . immunostaining was quantified using color video image analysis . results : The overall probability of paired biopsies from the same RA knee joint being significantly different from each other due to sampling variation was at most 22 for cytokine staining ( usually less than 10 ) . there were no significant differences between intrabiopsy and interbiopsy variability for cell adhesion molecule staining of the sublining and vessels . conclusion : The variability in cytokine and …

Interleukin 1 receptor antagonist anakinra ( kineret ) for treatment of rheumatic arthritis New treatment strategies in rheumatoid arthritis are … (2003 Aug)
interleukin 1 receptor antagonist anakinra ( kineret ) for treatment of rheumatic arthritis New treatment strategies in rheumatoid arthritis are targeted to interfere with critical mediators of inflammation . proinflammatory cytokines like IL 1 beta and tnfalpha play a crucial role in induction and maintenance of synovitis , pannus formation and bone and cartilage destruction . within a few years , these morphological changes may lead to joint destruction and consecutively to functional impairment . since april 2002 a recombinant human interleukin 1 receptor antagonist ( anakinra ) is available in germany for treatment of patients with rheumatoid arthritis . anakinra ( kineret ( R ) ) is approved for therapy in combination with methotrexate and should be applied according to guidelines established by the german rheumatology society for the use of biologicals in treatment of patients with rheumatoid arthritis . The approval of anakinra as a new therapeutic is based on data obtained in large multicenter , placebo controlled , and randomised trials in comparison to placebo . treatment of anakinra as monotherapy or in combination with methotrexate lead to significant improvement of signs and symptoms of disease as measured by the ACR 20 ( or more ) response and was associated with a slower radiographic progression with regard to joint space narrowing and development of erosions . anakinra showed a favourable safety profile with injection side reactions as the predominant side effect that occurs in 70 of patients usually after 10 12 days of treatment and that are …

Autologous interleukin 1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled … (2008 Apr)
autologous interleukin 1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial . introduction : incubation of blood with CrSO ( 4 ) coated glass beads stimulates the synthesis of anti inflammatory cytokines , such as interleukin 1 receptor antagonist ( IL 1ra ) , IL 4 , IL 10 , and IL 13 . As IL 1beta is thought to play a key role in the development of osteoarthritis ( OA ) , this product , also known as orthokin , might be a viable treatment for symptomatic knee OA . The aim of the current study was to evaluate the efficacy of orthokin for treatment of symptomatic knee OA in a randomized , multicentre , double blind , placebo controlled trial . patients AND methods : One hundred and sixty seven patients received six intra articular injections either with orthokin or physiological saline . The primary efficacy objective consisted of 30 superiority on the western ontario and mcmaster universities osteoarthritis index ( womac ) at 3 , 6 , 9 , and 12 months post treatment . additionally , the patients completed the visual analogue scale for pain , the Knee injury and osteoarthritis outcome score ( KOOS ) and Knee society clinical rating system . results : orthokin and placebo treatment resulted in similar improvements on the womac ( 16 . 8 vs 16 . 5 , respectively ; n . s . ) . orthokin resulted in …

Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. (1996 Oct)
modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures . comparison of monoclonal anti TNF alpha antibody with the interleukin 1 receptor antagonist . while there is an extensive literature on cytokine regulation in vivo using human cell lines or peripheral blood monocytes , very little is known about cytokine regulation within the multicellular environment of inflammatory sites in vivo . We have previously shown that in rheumatoid synovial membrane cultures , a complex , but pathophysiologically relevant mixture of cells , the addition of a neutralizing anti TNF alpha antibody inhibits the production of IL 1 and GM CSF , indicating the presence of a cytokine cascade in this inflammatory tissue . In this paper we demonstrate that the interactivities between cytokines in rheumatoid arthritis also extends to other cytokines , such as IL 6 and IL 8 , and that within the IL 1 family it is IL 1 beta in particular which is downregulated by neutralizing TNF alpha activity . The cytokine interactions are unidirectional , in that neutralization of TNF alpha reduced IL 1 beta , IL 6 and IL 8 production , whereas treatment of the rheumatoid synovial membrane cells with a neutralizing concentration of the IL 1 receptor antagonist ( IL 1ra ) reduced IL 6 and IL 8 production but not TNF alpha production . these results suggest a rationale for the profound anti inflammatory effects and consequent clinical benefit noted in RA patients treated recently in clinical trials with a …

Analysis of the inflammatory cytokine network among TNF alpha , IL 1 beta , IL 1 receptor antagonist , and … (1997 Jun)
analysis of the inflammatory cytokine network among TNF alpha , IL 1 beta , IL 1 receptor antagonist , and IL 8 in LPS induced rabbit arthritis . We investigated the cytokine network in rabbit lipopolysaccharide ( LPS ) induced arthritis , using inhibitors against homologous TNF alpha , IL 1 beta , and IL 8 . rabbits were intraarticularly injected with LPS ( 10 ng ) and cytokine inhibitors ( 10 micrograms each ) , and the concentrations of each cytokine in the synovial fluids were measured . maximum levels of TNF alpha and IL 8 were detected at 2 hours after LPS injection , whereas IL 1 beta and IL 1 receptor antagonist ( IL 1Ra ) were detected at 6 and 9 hours , respectively . By immunohistochemistry , synovial lining cells were positive for TNF alpha and IL 8 , and infiltrating leukocytes were positive for IL 1 beta and IL 1 Ra . The effects of cytokine inhibitors on the release of each cytokine were then investigated . The maximum levels of TNF alpha and IL 8 were not affected by blocking the activities of other cytokines . In contrast , the peak concentration of IL 1 beta was reduced by anti TNF alpha monoclonal Ab ( mAb ) , IL 1 Ra or anti IL 8 IgG . Peak concentrations of IL 1Ra were reduced by anti TNF alpha mAb or anti IL 8 IgG . Anti TNF alpha mAb , IL 1Ra , …

Specific interleukin 1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. (1987 Dec)
specific interleukin 1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis . interleukin 1 ( IL 1 ) activity and inhibition were studied in serum and urine from nine patients with systemic juvenile chronic arthritis ( S JCA ) . In afebrile patients IL 1 activity was normal or high . serum from two afebrile S JCA patients taken during a period of severe disease activity had an enhancing effect on the activity of exogenous IL 1 . secondary amyloidosis subsequently developed in one of these patients . In contrast , in febrile patients serum and urine IL 1 activity was low , apparently reflecting the presence of a strong inhibitor of IL 1 activity measured by the inhibition of prostaglandin E2 production by synovial cells . This inhibition was greatest at the time of peak temperature , suggesting the possibility of feedback regulation during fever . This novel identification in S JCA of a specific IL 1 inhibitor that competes at the IL 1 receptor level may be an important step in the understanding of the pattern of fever and the evaluation of disease in patients with S JCA .

A comparative study of the inhibitory effects of interleukin 1 receptor antagonist following administration as a recombinant protein or by … (2003 Aug)
A comparative study of the inhibitory effects of interleukin 1 receptor antagonist following administration as a recombinant protein or by gene transfer . anakinra , the recombinant form of IL 1 receptor antagonist ( IL 1Ra ) , has been approved for clinical use in the treatment of rheumatoid arthritis as the drug kineret trade mark , but it must be administered daily by subcutaneous injection . Gene transfer may offer a more effective means of delivery . In this study , using prostaglandin E2 production as a measure of stimulation , we quantitatively compared the ability of anakinra , as well as that of IL 1Ra delivered by gene transfer , to inhibit the biologic actions of IL 1beta . human synovial fibroblast cultures were incubated with a range of doses of anakinra or HIG 82 cells genetically modified to constitutively express IL 1Ra . The cultures were then challenged with recombinant human IL 1beta either simultaneously with addition of the source of IL 1Ra or 24 hours later . In a similar manner , the potencies of the two sources of IL 1Ra were compared when human synovial fibroblasts were challenged with IL 1beta produced constitutively by genetically modified cells . No significant difference in inhibitory activity was observed between recombinant protein and IL 1Ra provided by the genetically modified cells , under static culture conditions , even following incubation for 4 days . however , under culture conditions that provided progressive dilution of the culture media , …

Focal adhesion kinase and mitogen activated protein kinases are involved in chondrocyte activation by the 29 kDa amino terminal fibronectin … (2002 Jan)
focal adhesion kinase and mitogen activated protein kinases are involved in chondrocyte activation by the 29 kDa amino terminal fibronectin fragment . The 29 kDa amino terminal fibronectin fragment ( FN f ) has a potent chondrolytic effect and is thought to be involved in cartilage degradation in arthritis . however , little is known about signal transduction pathways that are activated by FN f . Here we demonstrated that FN f induced nitric oxide ( NO ) production from human articular chondrocytes . expression of inducible nitric oxide synthase ( iNOS ) mRNA and NO production were observed at 6 and 48 h after FN f treatment , respectively . interleukin 1beta ( IL 1beta ) mRNA up regulation was stimulated by FN f in human chondrocytes . To address the possibility that FN f induced NO release is mediated by IL 1beta production , the effect of IL 1 receptor antagonist ( IL 1ra ) was determined . IL 1ra partially inhibited FN f induced NO release although it almost completely inhibited IL 1beta induced NO release . tyrosine phosphorylation of focal adhesion kinase was induced transiently by FN f treatment . blocking antibodies to alpha ( 5 ) or beta ( 1 ) integrin and Arg Gly Asp containing peptides did not inhibit FN f induced NO production . PP2 , a Src family kinase inhibitor , or cytochalasin D , which selectively disrupts the network of actin filaments , inhibited both FAK phosphorylation and NO production …

Role of interleukin 4 and interleukin 10 in murine collagen induced arthritis. (1997 Mar)
Role of interleukin 4 and interleukin 10 in murine collagen induced arthritis . protective effect of interleukin 4 and interleukin 10 treatment on cartilage destruction . objective : To examine the role of endogenous interleukin 4 ( IL 4 ) and interleukin 10 ( IL 10 ) and the therapeutic effect of the addition of IL 4 and IL 10 in early and established murine collagen induced arthritis ( CIA ) . methods : murine recombinant IL 4 , IL 10 , or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7 10 days of CIA in DBA / 1 mice . Anti IL 4 , anti IL 10 , or both antibodies were given intraperitoneally before or after the onset of CIA . The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring . histology and reverse transcription polymerase chain reaction ( RT PCR ) analyses were performed at the end of the treatment period . results : IL 4 alone did not provoke any effect , IL 10 slightly suppressed the arthritis , but a more pronounced amelioration was found with the combination . This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset . apart from suppression of macroscopic signs of inflammation , combined treatment with IL 4 / IL 10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against …

IL 1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. (1992 Aug)
IL 1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium . IL 1 can participate in the perpetuation of arthritis through direct stimulation of synoviocytes and augmentation of matrix degradation . hence , local production of the IL 1R antagonist protein ( IRAP ) might be an important negative feedback signal that regulates synovitis . We assessed synovial IRAP production in synovia from 30 individuals , by using a specific mAb and the immunoperoxidase staining method . IRAP was detected in 11 of 12 rheumatoid arthritis ( RA ) synovial tissues ( ST ) and was located primarily in the sublining , particularly in perivascular regions enriched for macrophages . Some staining was observed in the intimal lining of the synovium , although this was significantly less than in the sublining ( p less than 0 . 05 ) . Nine of 12 osteoarthritis ( OA ) tissues were positive for IRAP . In contrast to RA , the staining was observed primarily in the synovial lining in OA , with only minimal sublining IRAP being detected . synovia from four patients without arthritis were negative ( three autopsy specimens and one post traumatic sample ) . Of the other two patients with miscellaneous diagnoses , one sample was negative ( tenosynovitis ) and one was positive ( seronegative inflammatory arthritis ) ( sublining ) . studies of serial sections and double immunostaining experiments indicated that macrophages are the major cells containing immunoreactive IRAP . …

The cytochrome P 450 dependent mono oxygenase system of the liver and interleukin 1 production by the macrophages in adjuvant … (1995 Jul)
The cytochrome P 450 dependent mono oxygenase system of the liver and interleukin 1 production by the macrophages in adjuvant arthritis in rats under the influence of beta carotene A relationship between the production of interleukin 1 ( IL 1 ) by macrophages from adjuvant induced arthritic rats and cytochrome P 450 dependent hepatic microsomal monooxygenase was studied . The synthesis of IL 1 by splenic and peritoneal macrophages on day 17 postadjuvant treatment was not altered , but the hepatic cytochrome P 450 levels and monooxygenase activity were significantly decreased . Beta carotene treatment of arthritic rats reduced hind paw swelling and concurrently stimulated the ability of macrophages to secrete IL 1 and increased the cytochrome P 450 levels and the activity of hepatic monooxygenase . The findings did not establish a definite relationship between the production of IL 1 by systemic macrophages on the one hand , and the hepatic cytochrome P 450 levels a and monooxygenase activity on the other hand . It thus appears that IL1 is unable to play a role of a mediator between the immune system and the hepatic cytochrome P 450 dependent monooxygenase system of rats with adjuvant induced arthritis .

Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte / macrophage colony stimulating factor … (1992 Sep)
human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte / macrophage colony stimulating factor and tumor necrosis factor alpha . neutrophils , an abundant cell type at sites of inflammation , have the ability to produce a number of cytokines , including interleukin 1 ( IL 1 ) , IL 8 , granulocyte macrophage colony stimulating factor ( GM CSF ) , and tumor necrosis factor alpha ( TNF alpha ) . In this study , we have examined the ability of human neutrophils to produce the IL 1 receptor antagonist ( IL 1Ra ) , a 17 23 kD protein recently isolated and cloned from macrophages . since IL 1Ra has been shown to inhibit both the in vitro and in vivo effects of IL 1 , its production by large numbers of tissue invading neutrophils might provide a mechanism by which the effects of IL 1 are regulated in inflammation . using antibodies that are specific for IL 1Ra and a cDNA probe encoding for this protein , we were able to show that neutrophils constitutively produce IL 1Ra . however , after activation by GM CSF and TNF alpha , IL 1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils . None of a large array of other potent neutrophil agonists were found to affect the production of IL 1Ra by neutrophils . quantitative measurements by enzyme linked immunosorbent assay revealed …

The function of the soluble interleukin 6 ( IL 6 ) receptor in vivo : sensitization of human soluble IL … (1996 Aug)
The function of the soluble interleukin 6 ( IL 6 ) receptor in vivo : sensitization of human soluble IL 6 receptor transgenic mice towards IL 6 and prolongation of the plasma half life of IL 6 . interleukin 6 ( IL 6 ) is considered an important mediator of acute inflammatory responses . moreover , IL 6 functions as a differentiation and growth factor of hematopoietic precursor cells , B cells , T cells , keratinocytes , neuronal cells , osteoclasts , and endothelial cells . IL 6 exhibits its action via a receptor complex consisting of a specific IL 6 receptor ( IL 6R ) and a signal transducing subunit ( gp130 ) . soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome , rheumatoid arthritis , and others . The function of the soluble ( s ) IL 6R in vivo is unknown . since human ( h ) IL 6 acts on human and murine target cells , but murine IL 6 on murine cells only , we constructed transgenic mice expressing the hsIL 6R . We report here that in the presence of hsIL 6R , mice are hypersensitized towards hIL 6 , mounting an acute phase protein gene induction at significantly lower IL 6 dosages compared to control animals . furthermore , in hsIL 6R transgenic mice , the detected acute phase response persists for a longer period of …

Cytokine mRNA in the joints and draining lymph nodes of rats with adjuvant arthritis and effects of cyclosporin A. (2000 Dec)
cytokine mRNA in the joints and draining lymph nodes of rats with adjuvant arthritis and effects of cyclosporin A . TNF alpha and IL 1beta promote leukocyte recruitment to arthritic joints and may contribute to cartilage degradation while regulatory cytokines such as IL 4 and IL 1RA may in part determine the course of arthritis . Here we report the pattern of TNF alpha , IL 1beta , IL 6 , IFN gamma , IL 1RA , and IL 4 mRNA expression , detected by RT / PCR , in the talar joint and draining popliteal lymph node ( PLN ) of rats with adjuvant arthritis ( AA ) . levels of TNF alpha and IFN gamma mRNA were increased in the PLN before clinical signs of arthritis . This was followed by increases in IL 1beta and IL 1RA mRNA at d9 and IL 6 mRNA at d12 . PLN IL 1RA mRNA levels were positively correlated with those of IL 1beta and TNF alpha throughout d5 d20 . IL 4 mRNA levels were highest on days 7 and 20 . In the synovium , a small increase in TNF alpha , IL 1beta , and IL 6 mRNA was detected on d5 then again on d12 . maximal synovial TNF alpha levels were reached on d20 , while IL 1beta peak expression was on d16 and IL 6 on d14 . IL 4 , IL 1RA , and IFN gamma mRNA was undetectable in the synovium . cyclosporin …

Live borrelia burgdorferi preferentially activate interleukin 1 beta gene expression and protein synthesis over the interleukin 1 receptor antagonist. (1992 Oct)
Live borrelia burgdorferi preferentially activate interleukin 1 beta gene expression and protein synthesis over the interleukin 1 receptor antagonist . Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty . because cytokines are thought to contribute to the pathogenesis of chronic arthritis , we investigated the effect of the Lyme disease spirochete , borrelia burgdorferi , on the gene expression and synthesis of IL 1 beta and the IL 1 receptor antagonist ( IL 1ra ) in human peripheral blood mononuclear cells . Live B . burgdorferi induced fivefold more IL 1 beta than IL 1 alpha and sevenfold more IL 1 beta than IL 1ra ; LPS or sonicated B . burgdorferi induced similar amounts of all three cytokines . This preferential induction of IL 1 beta was most dramatic in response to a low passage , virulent preparation of B . burgdorferi vs . three high passage avirulent strains . No difference in induction of IL 1ra was seen between these strains . The marked induction of IL 1 beta was partially diminished by heat treatment and abrogated by sonication ; IL 1ra was not affected . This suggested that a membrane component ( s ) accounted for the preferential induction of IL 1 beta . however , recombinant outer surface protein beta induced little IL 1 beta . By 4 h after stimulation , B . burgdorferi induced sixfold more IL 1 beta protein than LPS . …

Therapeutic strategies to reduce IL 1 activity in treating local and systemic inflammation. (2004 Jul)
therapeutic strategies to reduce IL 1 activity in treating local and systemic inflammation . All biological agents currently used for reducing tnfalpha activity in disease are neutralization strategies ; however , there are several strategies for reducing interleukin ( IL ) 1 activities : the IL 1 receptor antagonist ( IL 1Ra ) , anti IL 1beta monoclonal antibodies , the IL 1 Trap , IL 1 receptor type I antibodies , antibodies to the IL 1 receptor accessory chain and inhibitors of IL 1beta converting enzyme , now termed caspase 1 . In fact , caspase 1 inhibitors are the first orally active agents that target cytokines , as these inhibitors prevent the processing and release of active forms for IL 1beta and IL 18 , which is a member of the IL 1 family . The IL 1 Trap is a new concept in using soluble forms of cytokine receptors to bind and neutralize a specific cytokine . The Trap takes advantage of the high affinity of the two signaling chains of the cell surface IL 1 receptor linked by the Fc portion of IgG1 . The IL 1Ra is currently approved to treat rheumatoid arthritis ; in over 75 000 patients , the IL 1Ra has provided insights into the role of IL 1 in local and systemic inflammation , as well as the safety of long term reduction of IL 1 activity .