Delivery of biologically active anti inflammatory cytokines IL 10 and IL 1ra in vivo by the shigella type III secretion … (2008 Mar)
delivery of biologically active anti inflammatory cytokines IL 10 and IL 1ra in vivo by the shigella type III secretion apparatus . pathogenicity of many Gram negative bacteria relies on a type III secretion ( T3S ) apparatus , which is used for delivery of bacterial effectors into the host cell cytoplasm allowing the bacteria to manipulate host cell cytoskeleton network as well as to interfere with intracellular signaling pathways . In this study , we investigated the potential of the shigella flexneri T3SA as an in vivo delivery system for biologically active molecules such as cytokines . The anti inflammatory cytokines IL 10 and IL 1 receptor antagonist ( IL 1ra ) were genetically fused to the first 30 or 60 residues of the shigella T3S effector ipah9 . 8 or to the first 50 residues of the yersinia enterocolitica effector YopE and the recombinant fusion proteins were expressed in S . flexneri . YopE ( 50 ) IL 10 , IpaH ( 60 ) IL 10 , and IpaH ( 60 ) IL 1ra were efficiently secreted via the T3S apparatus of shigella . moreover , these recombinant proteins did not impair the invasive ability of the bacteria in vitro . In a murine model , shigella strains expressing YopE ( 50 ) IL 10 , IpaH ( 60 ) IL 10 , and IpaH ( 60 ) IL 1ra induced a lower mortality in mice that was associated with reduced inflammation and a restricted localization of bacteria …

Comparison of peripheral blood leukocyte kinetics after live escherichia coli , endotoxin , or interleukin 1 alpha administration. (1993 Aug)
comparison of peripheral blood leukocyte kinetics after live escherichia coli , endotoxin , or interleukin 1 alpha administration . studies using a novel interleukin 1 receptor antagonist . objective : This study was undertaken to evaluate whether hematologic and immunologic effects observed after bacteremia and endotoxemia in the host could be replicated by administration of recombinant human interleukin 1 alpha ( IL 1 alpha ) in a primate model . furthermore , to determine whether endogenously produced interleukin 1 ( IL 1 ) contributes to the changes observed during endotoxemia or gram negative septic shock , a specific IL 1 receptor antagonist ( IL 1 ra ) was administered . summary background DATA : The lipopolysaccharide ( LPS ) component of the outer membrane of gram negative bacteria initiates a constellation of metabolic and immunologic host responses . IL 1 , a macrophage derived cytokine , acts as a key mediator in the host response to infection and inflammation . methods : baboons were randomly assigned to receive either recombinant human IL 1 alpha , LPS , or live escherichia coli both with or without concomitant administration of IL 1ra . blood was collected hourly and analyzed using flow cytometric techniques . results : Both endotoxemia and live E . coli bacteremia induced an acute granulocytopenia ; however , the granulocytopenia gradually resolved in the endotoxemic group , but was sustained in the bacteremic group . An early lymphopenia and monocytopenia was elicited by LPS or E . coli and …

Tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. (1994 May)
tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats . background / AIMS : subserosal injection of purified group A streptococcal peptidoglycan polysaccharide ( PG APS ) induces chronic relapsing granulomatous enterocolitis and systemic inflammation in susceptible inbred lewis rats but only transient intestinal injury in buffalo and fischer rats . cecal interleukin 1 ( IL 1 ) and IL 1 receptor antagonist ( IL 1ra ) expression was measured in inbred rats displaying differential susceptibility to experimental enterocolitis . methods : The ileum and cecum of lewis , buffalo , and fischer rats were subserosally injected with purified PG APS or albumin . IL 1 and IL 1ra messenger RNA ( mRNA ) and protein ( IL 1 only ) were measured 1 or 27 days later . PG APS injected lewis rats were treated with recombinant human IL 1ra . kinetics of IL 1 and IL 1ra mRNA expression were studied in peritoneal cells . results : All rats strains developed acute inflammation with increased cecal concentrations of IL 1 beta and IL 1ra mRNA . lewis rats developed chronic enterocolitis and had higher IL 1 and IL 1ra mRNA tissue levels than buffalo or fischer rats , which displayed no chronic inflammation . IL 1 beta and IL 1ra were produced by submucosal granulomas and correlated with inflammation . IL 1 alpha protein levels paralleled IL 1 beta mRNA expression . IL 1ra treatment attenuated acute and chronic enterocolitis , …

Substance P stimulated interleukin 8 expression in human colonic epithelial cells involves protein kinase cdelta activation. (2005 Aug)
substance P stimulated interleukin 8 expression in human colonic epithelial cells involves protein kinase cdelta activation . substance P ( SP ) participates in acute intestinal inflammation via binding to the G protein coupled neurokinin 1 receptor ( NK 1R ) and release of nuclear factor kappa B ( NF kappab ) driven proinflammatory cytokines from colonic epithelial cells . however , the signal transduction pathways by which SP NK 1R interaction induces NF kappab activation and interleukin 8 ( IL 8 ) production are not clear . Here , we examined participation of protein kinase C ( PKC ) in SP induced IL 8 production in human nontransformed ncm460 colonocytes stably transfected with the human NK 1R ( ncm460 NK 1R cells ) . SP ( 10 ( 7 ) M ) induced an early ( 1 min ) phosphorylation of the PKC isoforms pkcdelta , PKC , and pkcepsilon , followed by I kappab kinase , ikappabalpha , and p65 phosphorylation . depletion of PKC by phorbol 12 myristate 13 acetate ( 10 microm ) blocked SP induced ikappabalpha and p65 phosphorylation and IL 8 production . The pkcdelta inhibitor rottlerin at a low concentration ( 1 microm ) , but not pseudosubstrate PKC and pkcepsilon inhibitors ( 10 microm ) , significantly reduced IL 8 secretion . pkcdelta silencing by RNA interference reduced pkcdelta protein expression and SP induced pkcdelta phosphorylation that was associated with diminished IL 8 promoter and NF kappab luciferase activities in response to …

Identification of IL 1 inhibitory activity as IL 1 receptor antagonist ( IL 1ra ) in vitro and kinetics of … (1995 Jul)
identification of IL 1 inhibitory activity as IL 1 receptor antagonist ( IL 1ra ) in vitro and kinetics of IL 1ra and IL 1 beta in experimental rabbit lung granuloma . This study investigated whether interleukin 1 ( IL 1 ) inhibitory activity in LPS stimulated culture supernatants of alveolar macrophages and epithelioid cells obtained from rabbit lung granulomas induced by complete freund s adjuvant ( CFA ) was identical to IL 1 receptor antagonist ( IL 1ra ) and examined the changes of IL 1ra and IL 1 beta levels in lung tissue during the natural course of granulomatous inflammation . In the thymocyte proliferation assay , prostaglandin E2 ( PGE2 ) free culture supernatants from each cell population revealed a bell shaped IL 1 titration curve with IL 1 activity suppressed at dilutions of 1 : 1 to 1 : 2 , and gel chromatography of serum free culture supernatants showed an IL 1 inhibitory peak at 21 25 kD . suppression of IL 1 activity in the supernatants at lower dilutions and the gel purified IL 1 inhibitory activity both almost disappeared after IL 1ra depletion with an anti rabbit IL 1ra immunoaffinity column , indicating that IL 1ra was responsible for this in vitro IL 1 inhibitory activity . pulmonary tissue levels of IL 1 beta pecked at 24 h ( 52 . 0 / 9 . 5 pg / mg ) after CFA injection , whereas IL 1ra levels peaked at 4 weeks ( …

Disturbance of oligodendrocyte development , hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide. (2003 Feb)
disturbance of oligodendrocyte development , hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide . increasing data provide support for the hypothesis that brain inflammation plays an important role in injury to developing white matter . In the present study , inflammatory responses in the neonatal rat brain were investigated following lipopolysaccharide ( LPS ) administration at postnatal day 5 . LPS induced brain injury was examined in brain sections 24 h , 3 and 9 days after LPS injection . white matter rarefaction was observed in 50 of the rat brains ( three out of six ) 24 h after LPS injection . lateral ventricle enlargement was found in 100 ( four out of four ) and 89 ( eight out of nine ) of rat brains 3 and 9 days after LPS administration , respectively . white matter necrosis was found in three out of nine brains injected with LPS on P14 . None of these injuries was observed in any control rat brains . No histological changes in gray matter were noted in the LPS injected rat brain . proinflammatory cytokines , tumor necrosis factor alpha ( tnfalpha ) , interleukin 1beta ( IL 1beta ) and interleukin 6 ( IL 6 ) , and inducible nitric oxide synthase ( iNOS ) in the rat brain were greatly induced after LPS administration . activated astrocytes and microglia / macrophages were found in the affected rat brains . double labeling showed that …

Interleukin 1 and occlusive arterial diseases. (2006 Jul)
interleukin 1 and occlusive arterial diseases . interleukin ( IL ) 1 is a pro inflammatory cytokine and a central mediator in the cytokine network , and is known to control important functions both in the immune system and inflammation . The activity of IL 1 is counter regulated by its endogenous inhibitor , IL 1 receptor antagonist ( IL 1Ra ) . IL 1 and IL 1Ra are produced and secreted by a variety of cells including those responsible for controlling immunity . A recent study indicated that IL 1 and IL 1Ra transcripts were expressed in the vessel wall , suggesting that these cytokines contribute to the development and progression of vascular diseases . In this review , we will discuss the recent advances in our understanding of the mechanism of action of IL 1 in occlusive arterial diseases such as neointimal hyperplasia and atherosclerosis , specifically in a mouse model .

The proinflammatory cytokines interleukin 1 and tumor necrosis factor and treatment of the septic shock syndrome. (1991 Jul)
The proinflammatory cytokines interleukin 1 and tumor necrosis factor and treatment of the septic shock syndrome . treating the septic shock syndrome with antibodies that block only endotoxin has its limitations . other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a , platelet activating factor antagonists , and blockade of endothelial cell leukocyte adhesion molecules . specific blockade of the proinflammatory cytokines interleukin 1 ( IL 1 ) or tumor necrosis factor ( TNF ) reduces the morbidity and mortality associated with septic shock . moreover , blocking IL 1 and TNF likely has uses in treating diseases other than septic shock . Use of neutralizing antibodies to TNF or to IL 1 receptors have reduced the consequences of infection and inflammation , including lethal outcomes in animal models . The IL 1 receptor antagonist , a natural occurring cytokine , blocks shock and death due to escherichia coli and ameliorates a variety of inflammatory diseases . soluble TNF and IL 1 surface receptors , which bind their respective cytokines , also ameliorate disease processes . current clinical trials are evaluating the safety and efficacy of these anticytokine therapies either alone or together .

The role of IL 1 and IL 1Ra in joint inflammation and cartilage degradation. (2006 Oct)
The role of IL 1 and IL 1Ra in joint inflammation and cartilage degradation . interleukin ( IL ) 1 is a cytokine that plays a major role in inflammatory responses in the context of infections and immune mediated diseases . IL 1 refers to two different cytokines , termed IL 1alpha and IL 1beta , produced from two genes . IL 1alpha and IL 1beta are produced by different cell types following stimulation by bacterial products , cytokines , and immune complexes . monocytes / macrophages are the primary source of IL 1beta . Both cytokines do not possess leader peptide sequences and do not follow a classical secretory pathway . IL 1alpha is mainly cell associated , whereas IL 1beta can be released from activated cells after cleavage of its amino terminal region by caspase 1 . IL 1 is present in the synovial tissue and fluids of patients with rheumatoid arthritis . several in vitro studies have shown that IL 1 stimulates the production of mediators such as prostaglandin E ( 2 ) , nitric oxide , cytokines , chemokines , and adhesion molecules that are involved in articular inflammation . furthermore , IL 1 stimulates the synthesis and activity of matrix metalloproteinases and other enzymes involved in cartilage destruction in rheumatoid arthritis and osteoarthritis . The effects of IL 1 are inhibited in vitro and in vivo by natural inhibitors such as IL 1 receptor antagonist and soluble receptors . IL 1 receptor antagonist belongs to …

Endotoxin and interleukin 1 related hepatic inflammatory response promotes liver failure after partial hepatectomy. (1995 Dec)
endotoxin and interleukin 1 related hepatic inflammatory response promotes liver failure after partial hepatectomy . impairment of various functions of the liver and concomitantly increased levels of parameters of liver damage , a clinical entity termed liver failure , is commonly seen after partial hepatectomy . We investigated in a rat model whether damage of the remnant liver was due to local inflammatory responses , and related to endotoxin or interleukin 1 ( IL 1 ) . To address this question , the effects of partial hepatectomy on infiltration of immunocompetent cells and expression of major histocompatibility complex ( MHC ) class II antigen of macrophages in the remnant liver was studied using immunohistochemical techniques . specific intervention with recombinant N terminal bactericidal / permeability increasing protein ( rbpi23 ) to neutralize endotoxin and with IL 1 receptor antagonist ( IL 1ra ) to block IL 1 activity was used to examine the respective roles of endotoxin and IL 1 . after partial hepatectomy , we found an influx of neutrophils , an increased expression of MHC class II antigens , and morphologic changes of kupffer cells consistent with activation . these inflammatory events coincided with increased serum levels of markers of liver damage ( aspartate aminotransferase , alanine aminotransferase , ammonia ) . Both neutralization of endotoxin and blocking of IL 1 activity reduced hepatic inflammation and reduced serum levels of aminotransferases and ammonia . In addition , liver cell proliferation as assessed by staining for proliferating cell nuclear …

Physiological significance of the interleukin 1 receptor accessory protein. (2002 Mar)
physiological significance of the interleukin 1 receptor accessory protein . interleukin 1 receptor accessory protein ( IL 1racp ) is an essential signal transducing component of the IL 1 receptor type I . The recent availability of IL 1racp deficient ( KO ) mice allows to study the in vivo function of IL 1racp . animals were injected intraperitoneally with rat recombinant IL 1beta ( 200 ng / mouse ) , lipopolysaccharide ( LPS , 5 microg / mouse ) , or subjected to 1 hour restraint stress . neuroendocrine and immune parameters were measured 2 h after IL 1 or LPS injection or just after restraint . In wild type controls , IL 1 and LPS activated the hypothalamic pituitary adrenal axis and increased plasma IL 6 . In KO mice , the plasma levels of corticosterone and IL 6 increased after LPS , but not after rat recombinant IL 1beta . The LPS induced depression of the lymphoproliferation was similar in wild type and KO mice . finally , the 1 hour restraint was able to increase the plasma levels of corticosterone in KO mice . these results show that IL 1racp is essential for physiological activities of peripheral IL 1 , as it was previously demonstrated for those of brain IL 1 . however , using IL 1racp KO mice , we were unable to demonstrate a specific role of endogenous IL 1 during LPS induced inflammation . moreover , stress induced activation of the hypothalamic pituitary …

Interleukin 1 receptor antagonist suppresses experimental autoimmune encephalomyelitis ( EAE ) in rats by influencing the activation and proliferation of … (1998 Jul)
interleukin 1 receptor antagonist suppresses experimental autoimmune encephalomyelitis ( EAE ) in rats by influencing the activation and proliferation of encephalitogenic cells . considering the role of pleiotropic interleukin 1 ( IL 1 ) in inflammation and autoimmunity , studies were designed to examine whether specific blockade of IL 1 may influence these processes in the CNS . although the role of CD4 T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis ( EAE ) has been unequivocally demonstrated , the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined . We have evaluated the effect of human recombinant interleukin 1 receptor antagonist ( IL 1Ra ) in vivo on the course of actively induced EAE in highly susceptible Dark agouti ( DA ) rats . The rats which were treated during the induction phase of disease ( days 0 6 ) with IL 1Ra ( 350 microg / rat / day ) developed milder signs of EAE , when compared to saline treated control animals immunized with encephalitogen , which developed severe single episode disease . The transfer of lymph node cells ( LNC ) isolated from MBP primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients . however , rats injected with LNC that have been stimulated in vitro in the presence of IL 1Ra ( 10 microg / ml ) developed …

Elevated levels of soluble interleukin 1 receptor type II and interleukin 1 receptor antagonist in patients with chronic arthritis : … (1998 Jul)
elevated levels of soluble interleukin 1 receptor type II and interleukin 1 receptor antagonist in patients with chronic arthritis : correlations with markers of inflammation and joint destruction . objective : To compare plasma levels of interleukin 1 receptor antagonist ( IL 1Ra ) , soluble IL 1 receptor type I ( sIL 1RI ) , and soluble IL 1 receptor type II ( sIL 1RII ) in patients with chronic polyarthritis , and to establish correlations between levels of these naturally occurring IL 1 inhibitors and indices of disease activity and joint destruction . methods : levels of IL 1Ra , sIL 1RI , and sIL 1RII were measured in plasma samples from patients with chronic polyarthritis , using specific radioimmunoassays . levels were correlated with indices of disease activity and joint destruction . results : plasma levels of IL 1Ra , sIL 1RI , and sIL 1RII were significantly higher in polyarthritis patients than in controls . IL 1Ra levels correlated positively with all indices of disease activity and joint destruction ( P 0 . 0001 ) . In contrast , sIL 1RII levels correlated negatively with indices of joint destruction , such as the larsen score in the wrist ( P 0 . 04 ) . interestingly , sIL 1RII levels were higher in patients with nondestructive arthritis ( larsen score or 1 ) than in patients with destructive arthritis . levels of sIL 1RI did not correlate with indices of disease activity or joint destruction . …

The inhibitory effects of interleukin 1 on growth hormone action during catabolic illness. (2006 Oct)
The inhibitory effects of interleukin 1 on growth hormone action during catabolic illness . growth hormone ( GH ) induces the expression of the anabolic genes responsible for growth , metabolism , and differentiation . normally , GH stimulates the synthesis of circulating insulin like growth factor I ( IGF I ) by liver , which upregulates protein synthesis in many tissues . The development of GH resistance during catabolic illness or inflammation contributes to loss of body protein , resulting in multiple complications that prolong recovery and cause death . In septic patients , increased levels of proinflammatory cytokines and GH resistance are commonly observed together . numerous studies have provided evidence that the inhibitory effects of cytokines on skeletal muscle protein synthesis during sepsis and inflammation are mediated indirectly by changes in the GH / IGF I system . interleukin ( IL ) 1 , a member of the family of proinflammatory cytokines , interacts with most cell types and is an important mediator of the inflammatory response . infusion of a specific IL 1 receptor antagonist ( IL 1Ra ) ameliorates protein catabolism and GH resistance during systemic infection . This suggests that IL 1 is an important mediator of GH resistance during systemic infection or inflammation . consequently , a better understanding of the interaction between GH , IL 1 , and the regulation of protein metabolism is of great importance for the care of the patient .

Lipopolysaccharide directly stimulates the intrapituitary interleukin 6 production by folliculostellate cells via specific receptors and the p38alpha mitogen activated protein … (2000 Dec)
lipopolysaccharide directly stimulates the intrapituitary interleukin 6 production by folliculostellate cells via specific receptors and the p38alpha mitogen activated protein kinase / nuclear factor kappab pathway . bacterial lipopolysaccharide ( LPS ) activates the immune system and induces increases in peripheral cytokines , which , in turn , affect the endocrine system . In particular , LPS induced cytokines stimulate the hypothalamic pituitary adrenal axis to increase levels of antiinflammatory acting glucocorticoids . In the present work , we show that LPS directly stimulates interleukin ( IL ) 6 release by mouse pituitary folliculostellate ( FS ) TtT / GF tumor cells and FS cells of mouse pituitary cell cultures . The stimulatory effect of LPS was strongly enhanced in the presence of serum , suggesting that LPS is only fully active as a complex with LPS binding protein ( LBP ) . Both TtT / GF cells and mouse pituitaries expressed CD14 , which binds the LPS / LBP complex , and Toll like receptor type 4 , which induces LPS signals . LPS increased phospoinositol turnover in TtT / GF cells and induced phosphorylation of p38alpha mitogen activated protein kinase and the inhibitor ( ikappab ) of nuclear factor kappa B . nuclear factor kappa B was activated by LPS in TtT / GF cells . functional studies demonstrated that My4 ( an antibody blocking the interaction between LPS / LBP and CD14 ) , sb203580 , ( a specific inhibitor of p38alpha mitogen activated protein kinase phosphorylation …

Retinoic acid regulates differentially the expression of IL 1 beta and IL 1 receptor antagonist ( IL 1ra ) in … (1996 Aug)
retinoic acid regulates differentially the expression of IL 1 beta and IL 1 receptor antagonist ( IL 1ra ) in PMA activated human monocytes . retinoic acid ( RA ) is a well known immunological modulator . although it has been shown that RA stimulates IL 1 expression in monocytes , it is of interest for understanding of the regulatory role of RA in inflammation to examine whether RA also modulates the expression of the IL 1 receptor antagonist ( IL 1ra ) , which is reported to reduce IL 1 beta mediated inflammation . In this study , we examined the effect of RA on expression of IL 1 beta and IL ra in phorbol myristate acetate ( PMA ) activated human monocytes . RA enhanced gene expression and production of IL 1 beta in PMA activated monocytes . however , interestingly , gene expression and production of IL 1ra in the cells were markedly inhibited by RA . these results show that RA differentially regulates IL 1 beta and IL ra expression in PMA activated human monocytes and suggest that RA may promote IL 1 mediated inflammation .

Apoptosis : a target for potentiation of UV induced IL 1Ra synthesis by IVIg. (2007 May)
apoptosis : a target for potentiation of UV induced IL 1Ra synthesis by IVIg . IL 1Ra prevents IL 1 induced inflammatory signalling , a mechanism potentially important for several pathological conditions characterized by inflammation . When administered as a drug in the recombinant form , it displays a protective effect towards them . We postulated that this action could also be achieved by pharmacological activation of endogenous IL 1Ra production . We previously showed that photochemotherapy and UV light increased monocyte / macrophages IL 1Ra secretion . A similar effect has been shown for IVIg . The aim of this study was to define optimal in vitro conditions for induction of IL 1Ra secretion . As both agents induce lymphocytes apoptosis , we focused our analysis on the influence of IVIg on UV induced IL 1Ra production on this mechanism . after overnight preincubation at 37 degrees C , UV irradiated PBL mixed with two IVIg concentrations ( 1 and 25 mg / ml ) were cocultured with autologous PBMC . apoptosis was measured by annexin V / PI . IL 1Ra secretion was evaluated by RT PCR and luminex microbead array assay . A significant additive dose dependent influence of IVIg ( 85 ; p 0 . 0005 ) on UV induced IL 1Ra secretion , involved both Fc receptor activation at a low dose ( 1 mg / ml ) and a potent apoptotic action on PBL reinforcing the UV effect at high concentrations ( 25 mg …

Interleukin ( IL ) 1 receptor associated kinase ( IRAK ) requirement for optimal induction of multiple IL 1 signaling … (1998 Jul)
interleukin ( IL ) 1 receptor associated kinase ( IRAK ) requirement for optimal induction of multiple IL 1 signaling pathways and IL 6 production . interleukin ( IL ) 1 is a proinflammatory cytokine with pleiotropic effects in inflammation . IL 1 binding to its receptor triggers a cascade of signaling events , including activation of the stress activated mitogen activated protein ( MAP ) kinases , c Jun NH2 terminal kinase ( JNK ) and p38 MAP kinase , as well as transcription factor nuclear factor kappab ( NF kappab ) . IL 1 signaling results in cellular responses through induction of inflammatory gene products such as IL 6 . One of the earliest events in IL 1 signaling is the rapid interaction of IL 1 receptor associated kinases , IRAK and IRAK 2 , with the receptor complex . The relative roles of IRAK and IRAK 2 in IL 1 signaling pathways and subsequent cellular responses have not been previously determined . To evaluate the importance of IRAK in IL 1 signaling , IRAK deficient mouse fibroblast cells were prepared and studied . Here we report that IL 1 mediated activation of JNK , p38 , and NF kappab were all reduced in embryonic fibroblasts deficient in IRAK expression . In addition , IL 6 production in response to IL 1 was also dramatically reduced in IRAK deficient embryonic fibroblasts and in skin fibroblasts prepared from IRAK deficient mice . Our results demonstrate that IRAK plays an …

Absence of correlations between indices of systemic inflammation and synovial fluid interleukin 1 ( alpha and beta ) in rheumatic … (1990 Apr)
absence of correlations between indices of systemic inflammation and synovial fluid interleukin 1 ( alpha and beta ) in rheumatic diseases . there are two forms of the cytokine interleukin 1 ( IL1 ) , produced by two distinct genes encoding a neutral ( IL1 beta ) and an acidic ( IL1 alpha ) peptide . They have powerful pro inflammatory , immunopotentiating , catabolic and arthritogenic properties in vivo and have been implicated in the pathogenesis of rheumatic diseases . In this study , using specific immunoassays , we have measured both IL1 alpha and IL1 beta levels in synovial fluids ( SF ) from a large number of patients with different rheumatic diseases . biologically significant levels of both cytokines were found in SF from patients with different forms of arthritis , but no correlations were found with any of the measures of disease activity that we tested . We also describe the presence in joint exudates of biological inhibitor ( s ) that neutralize IL1 induced T cell activation . This is the first report of IL1 alpha and IL1 beta measurements in the same synovial exudates and also of the comparison of local levels of these cytokines with conventional indices of systemic inflammation .

Cytokine inhibitors in the treatment of rheumatoid arthritis. (2002 Mar)
cytokine inhibitors in the treatment of rheumatoid arthritis . rheumatoid arthritis ( RA ) is an immune mediated disease characterised by articular inflammation and subsequent tissue damage leading to severe disability and increased mortality . A variety of cytokines are produced locally in the rheumatoid joints . numerous studies have demonstrated that IL 1 and TNF alpha , two prototypic pro inflammatory cytokines , play an important role in the mechanisms involved in synovial inflammation and in progressive joint destruction . indeed , the administration of TNF alpha and IL 1 inhibitors in patients with RA led to a dramatic improvement of clinical and biological signs of inflammation and a reduction of radiological signs of bone erosion and cartilage destruction . however , despite these encouraging results , a significant percentage of patients do not respond to these agents , suggesting that other mediators are also involved in the pathophysiology of arthritis . This review describes the results of clinical trials with TNF alpha inhibitors and a specific IL 1 inhibitor ( IL 1 receptor antagonist IL 1Ra ) . In addition , other therapeutic strategies are also discussed .