Interleukin 1 deficient mice exhibit high sensitivity to gut derived sepsis caused by pseudomonas aeruginosa. (2005 Jun)
interleukin 1 deficient mice exhibit high sensitivity to gut derived sepsis caused by pseudomonas aeruginosa . background : The role of interleukin ( IL ) 1 in infectious diseases is controversial ; some investigators indicated an enhancing effect of IL 1 on host resistance whereas others demonstrated the protective role of IL 1 receptor antagonist in infection . We evaluated the role of endogenous IL 1 in gut derived sepsis caused by pseudomonas aeruginosa , by comparing IL 1 deficient mice and wild type ( WT ) mice . methods : Gut derived sepsis was induced by intraperitoneal injection of cyclophosphamide after colonization of P . aeruginosa strain D4 in the intestine . results : The survival rate of IL 1 deficient mice was significantly lower than that of WT mice ( P 0 . 01 ) . bacterial counts in the liver , mesenteric lymph node and blood were significantly higher in IL 1 deficient mice than in WT mice . tumor necrosis factor alpha and IL 6 in the liver were significantly higher in IL 1 deficient mice than in WT mice . In vitro , phagocytosis and cytokine production by macrophages were impaired in IL 1 deficient mice compared with WT mice . conclusion : Our results indicate a critical role for IL 1 during gut derived P . aeruginosa sepsis . The results also suggest that both impairment of cytokine production and phagocytosis by macrophages are caused by IL 1 deficiency and lead to impaired host …

Nitrite / nitrate oxide and cytokines changes in patients with surgical stress. (2005 May)
nitrite / nitrate oxide and cytokines changes in patients with surgical stress . nitric oxide ( NO ) produced by inducible nitric oxide synthase ( iNOS ) is implicated in immunological and inflammatory processes . inflammatory cytokines and endotoxin induce a large amount of NO from various cells . surgical stress produces cytokines , which leads to systemic inflammatory response syndrome ( SIRS ) . continuously high production of cytokines causes a variety of complications including pneumonia , intraabdominal abscess and sepsis . We investigated the relationships between the nitrite / nitrate ( NOx ) concentration and the level of cytokines in 50 patients undergoing gastroenterological surgery . We measured the levels of cytokines , including interleukin 6 ( IL 6 ) , tumor necrosis factor alpha ( TNF alpha ) interleukin 1 receptor antagonist ( IL 1ra ) , and nitrite / nitrate ( NOx ) concentration in the serum and exudative fluid from the thoracic or abdominal cavity of 50 patients undergoing gastroenterological surgery in order to make clear the relationship between cytokines and NO . NOx levels in the serum of the group with complications were higher on days 3 and 7 than in the group with no complications ( P 0 . 05 ) . In the complications group , IL 6 was more elevated , and the NOx level was synchronously elevated . In conclusion , surgical stress caused inflammatory cytokinemia . NOx was produced during surgical stress , and when complications occurred , more …

The cytokine response to strenuous exercise. (1999 Mar)
The cytokine response to strenuous exercise . strenuous exercise is accompanied by an increase in circulating proinflammatory and inflammation responsive cytokines , having some similarities with the response to sepsis and trauma . The sequential release of tumour necrosis factor alpha , interleukin ( IL ) 1 beta , IL 6 , and IL 1 receptor antagonist ( IL 1ra ) in the blood is comparable to that observed in relation to bacterial diseases . eccentric exercise is associated with an increase in serum IL 6 concentrations and is significantly correlated with the concentration of creatine kinase ( CK ) in the following days , whereas no changes are found after the concentric exercise ; this demonstrates a close association between exercise induced muscle damage and increased serum levels of IL 6 . The time course of cytokine production , the close association with muscle damage , and the finding of mRNA IL 6 in skeletal muscle biopsies after intense exercise all support the idea that during eccentric exercise myofibers are mechanically damaged and that this process stimulates the local production of inflammatory cytokines . It remains to be shown whether systemic endotoxemia during exercise is also a cause of elevated levels of cytokines in the plasma . The present review also discusses the possible roles of protein breakdown , delayed onset muscle soreness , and clinical implications of the acute phase response following exercise .

Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. (1995 Jul)
natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome . The sepsis intervention group . objective : To assess the value of measuring circulating concentrations of mediators ( endotoxin , tumor necrosis factor alpha TNF alpha , interleukin 1 beta IL 1 beta , and interleukin 6 IL 6 ) and their endogenous antagonists ( antiendotoxin core antibody endocab , interleukin 1 receptor antagonist IL 1ra , and soluble TNF receptors sTNF R ) in predicting mortality and organ failure in sepsis syndrome . design : cohort study with a follow up period of 30 days . setting : intensive therapy units of five tertiary referral centers in scotland . subjects : A total of 146 intensive therapy unit patients with sepsis syndrome underwent repeated sampling during a 10 day period following admission to an intensive therapy unit . MAIN outcome measures : circulating concentrations of mediators and antagonists were compared in survivors and nonsurvivors . results : median acute physiology and chronic health evaluation II score was 23 ( range , 8 to 40 ) . mortality at 30 days was 49 . On entry to the study , circulating endotoxin was detected in 66 of patients , TNF alpha in 14 , and IL 1 beta in 29 . levels did not predict mortality or organ failure . patients with IL 6 concentrations in excess of 3000 pg / mL had an increased mortality rate ( 64 vs 40 , P . 02 ) . The …

Inhibition of interleukin 22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. (2007 Mar)
inhibition of interleukin 22 attenuates bacterial load and organ failure during acute polymicrobial sepsis . interleukin 22 ( IL 22 ) is a recently discovered proinflammatory cytokine , structurally related to IL 10 . since IL 22 is induced by lipopolysaccharide in vivo , we studied the role of IL 22 in a model of polymicrobial peritonitis . quantitative real time reverse transcription PCR analysis showed marked induction of IL 22 and IL 22 receptor in spleen and kidney during the course of sepsis . The biological activity of IL 22 is modulated by IL 22 binding protein ( IL 22BP ) , which is considered a natural antagonist of IL 22 . To further analyze the role of IL 22 during septic peritonitis , mice were treated with recombinant IL 22BP generated as fcgamma2a fusion protein . IL 22BP Fc completely blocked IL 22 induced stat3 activation in hepatocytes in vitro . treatment of mice with IL 22BP Fc 4 h before sepsis induction led to enhanced accumulation of neutrophils and mononuclear phagocytes and a reduced bacterial load at the site of infection . In addition , IL 22 blockade led to an enhanced bacterial clearance in liver and kidney and reduced kidney injury . these results imply an important proinflammatory role of IL 22 during septic peritonitis , contributing to bacterial spread and organ failure . IL 22 therefore appears to play an important role in the regulation of inflammatory processes in vivo .

Association between IL 1ra gene polymorphism and premature delivery. (2004 Mar)
association between IL 1ra gene polymorphism and premature delivery . IL 1 receptor antagonist ( IL 1ra ) gene polymorphism was examined in 95 israeli preterm newborns and compared to that of adult volunteers . The genotype was determined using PCR amplification of the variable region of intron 2 of the IL 1ra gene . The IL 1raa1 allele was found to be predominant in the two groups . however , a significant higher frequency of IL 1raa2 allele was found in preterm newborns . The difference was mainly due to higher proportion of homozygous for IL 1raa2 in the preterm neonates ( 19 ) as compared with adults ( 7 ) . No such association could be demonstrated between IL 1raa2 allele and severe sepsis in preterm newborns . The frequency of IL 1raa2 allele among preterms with a septic episode did not differ significantly from that found in newborns without sepsis . The results suggest an association between the IL 1ra genotype and the incidence of premature delivery .

Plasma levels of interleukin 1 receptor antagonist ( IL 1ra ) and severity of illness in patients with burns. (1996 Dec)
plasma levels of interleukin 1 receptor antagonist ( IL 1ra ) and severity of illness in patients with burns . The present study was conducted to determine whether a plasma interleukin 1 receptor antagonist ( IL 1ra ) would reflect the severity of burn injury and to examine the relation between IL 1ra and the cytokines . We studied 24 burn patients in whom the total burn surface area ( TBSA ) accounted for at least 20 of the body surface , and in whom serial blood samples could be obtained beginning immediately after the burn injury . plasma levels of IL 1ra were determined by enzyme linked immunosorbent assay ( elisa ) . plasma levels of tumor necrosis factor alpha ( TNF alpha ) , IL 6 , and IL 8 were also determined by elisa . endotoxin was measured by an endotoxin specific synthetic substrate method . there was a significant correlation between the plasma levels of IL 1ra and TBSA during the first week following burn injury . The IL 1ra level was the highest immediately after the burn injury . The level decreased markedly thereafter , and again rose when infection occurred . The IL 1ra level was extraordinarily elevated in patients who developed concomitant sepsis , septic shock or the septic multiple organ dysfunction syndrome . The IL 1ra level on admission and the maximum IL 1ra level during the observation period were significantly higher in the patients who eventually died than in the survivors …

Limited involvement of interleukin 6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies … (1992 Nov)
limited involvement of interleukin 6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin 6 or its receptor in various murine models . several studies in human patients and in laboratory animals have revealed a correlation between serum interleukin ( IL ) 6 levels and outcome in clinical sepsis and in related animal models , respectively . In the present study , two monoclonal antibodies were used to investigate the contribution of IL 6 in the lethal action of tumor necrosis factor ( TNF ) and of lipopolysaccharide ( LPS ) in mice . We studied the potential protective properties of an anti murine ( m ) IL 6 antibody and of an anti mIL 6 receptor antibody . In controlled experiments , we observed that both monoclonal antibodies conferred a dose dependent protection to a lethal dose of mTNF . detailed studies with the monoclonal antibodies indicate , however , that protection was no longer observed when the mTNF dose was slightly higher than the lethal dose . likewise , the anti IL 6 monoclonal antibody protected against injections of LPS at a lethal dose concentration , but here too failed to protect against higher doses of LPS . The anti IL 6 monoclonal antibody was unable to protect against mTNF in mice sensitized by galactosamine , the corticoid receptor antagonist ru38486 or human ( h ) IL 1 beta . protection did not correlate with the serum concentrations of IL …

Effects of tumor necrosis factor and interleukin 1 on the constriction induced by angiotensin II in rat aorta. (1996 Dec)
effects of tumor necrosis factor and interleukin 1 on the constriction induced by angiotensin II in rat aorta . To better understand the different steps in the changes occurring in vascular reactivity during sepsis , we studied the effects of a short exposure to tumor necrosis factor ( TNF ) and interleukin 1 ( IL 1 ) on the contraction in response to angiotensin II ( ANG II ) . The contraction elicited by ANG II was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 25 ng / ml TNF or to 5 or 20 ng / ml IL 1 . This contraction was not significantly changed by TNF but was 109 / 23 and 190 / 38 greater than in control rings after 5 and 20 ng / ml IL 1 , respectively . because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins , we tested the hypothesis that IL 1 interferes with this modulation . We found that the IL 1 induced increase in contraction in response to ANG II was completely inhibited by 10 ( 5 ) M of the cyclooxygenase inhibitor indomethacin and also by 10 ( 5 ) M of the prostaglandin H2 / thromboxane A2 receptor antagonist SQ 29548 . Note , however , that in rings exposed to IL 1 the contraction in response to the thromboxane A2 receptor agonist U 46619 was not significantly different from the contraction in …

Superantigens from staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL … (2003 Dec)
superantigens from staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL 1 beta . background : staphylococcus aureus is one of the most common bacteria in human sepsis , a condition in which the activation of blood coagulation plays a critical pathophysiological role . during severe sepsis and septic shock microthrombi and multiorgan dysfunction are observed as a result of bacterial interference with the host defense and coagulation systems . objectives : In the present study , staphylococcal superantigens were tested for their ability to induce procoagulant activity and tissue factor ( TF ) expression in human whole blood and in peripheral blood mononuclear cells . methods AND results : determination of clotting time showed that enterotoxin A , B and toxic shock syndrome toxin 1 from S . aureus induce procoagulant activity in whole blood and in mononuclear cells . The procoagulant activity was dependent on the expression of TF in monocytes since antibodies to TF inhibited the effect of the toxins and TF was detected on the surface of monocytes by flow cytometry . In the supernatants from staphylococcal toxin stimulated mononuclear cells , interleukin ( IL ) 1 beta was detected by elisa . furthermore , the increased procoagulant activity and TF expression in monocytes induced by the staphylococcal toxins were inhibited in the presence of IL 1 receptor antagonist , a natural inhibitor of IL 1 beta . conclusions : The present study shows that superantigens from …

Recombinant interleukin 1 receptor antagonist ( IL 1ra ) : effective therapy against gram negative sepsis in rats. (1992 Aug)
recombinant interleukin 1 receptor antagonist ( IL 1ra ) : effective therapy against gram negative sepsis in rats . background : morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention . interleukin 1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis . The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin 1 receptor antagonist ( IL 1ra ) against polymicrobial gram negative septicemia in rats . methods : Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture ( CLP ) . after 3 hours rats received either IL 1ra ( 10 mg / kg intravenous bolus followed by 5 mg / kg / hr ) or an equal volume of vehicle intravenously for 24 hours . heart rate , respirations , mean arterial blood pressure , and temperature were recorded at frequent intervals , and survival was assessed for 30 hours after CLP . results : there were no differences in vital signs between groups at baseline or before treatment , and all animals appeared ill with huddled posture , piloerection , and hyperventilation . twenty four hours after CLP , IL 1ra significantly ameliorated bradycardia ( p 0 . 01 ) , hypothermia ( p 0 . 001 ) , and hypotension ( p 0 . 05 ) , and 30 hour survival was significantly improved ( 71 vs 20 , p …

Presence of high levels of leukocyte associated interleukin 8 upon cell activation and in patients with sepsis syndrome. (1997 Mar)
presence of high levels of leukocyte associated interleukin 8 upon cell activation and in patients with sepsis syndrome . In inflammatory and infectious diseases , the presence of circulating cytokines in plasma strongly suggests , following their exacerbated production , that saturation of specific binding sites has occurred or that an equilibrium between receptor bound and free cytokines has been reached . In this report , we demonstrate that in addition to circulating interleukin 8 ( IL 8 ) , high levels of cell associated IL 8 were detected in blood samples from patients with sepsis syndrome . The following analysis will reveal that in addition to erythrocytes , which have been dubbed a sink for IL 8 , peripheral blood mononuclear cells ( PBMC ) and polymorphonuclear cells ( PMN ) contributed to the detection of cell associated IL 8 . On a per cell basis , 2 , 000 to 7 , 000 times the amount of IL 8 was found associated with PMN than with erythrocytes . In addition , circulating cells may well be the source of the leukocyte associated form of IL 8 . similarly , in vitro experiments , such as whole blood stimulation assays or the addition of exogenous IL 8 in blood samples , demonstrated that a large proportion of the IL 8 was associated with leukocytes . This suggests that the trapping of free cytokines onto the cell surface and the internalization of the IL 8 bound to its receptor , …

Neuropeptide Y regulates catecholamine release evoked by interleukin 1beta in mouse chromaffin cells. (2007 Feb)
neuropeptide Y regulates catecholamine release evoked by interleukin 1beta in mouse chromaffin cells . activation of the hypothalamic pituitary adrenal gland ( HPA ) axis can modulate the immune system . cytokines and neuropeptide Y ( NPY ) are potent regulators of the HPA axis and are both produced by the adrenal medulla . The cytokine interleukin 1beta ( IL 1beta ) belongs to the interleukin 1 family along with interleukin 1alpha and the interleukin receptor antagonist ( IL 1ra ) . The aim of the present study was to determine the interaction between NPY and IL 1beta in catecholamine ( norepinephrine , NE and epinephrine , EP ) release from mouse chromaffin cells in culture . We found that IL 1beta increased the constitutive release of NPY , NE and EP from mouse chromaffin cells . This IL 1beta stimulatory effect was blocked by IL 1ra . The immunoneutralization of NPY and the use of the NPY Y ( 1 ) receptor antagonist ( BIBP 3226 ) inhibited the stimulatory effect of IL 1beta on catecholamine release from these cells . The present work shows that IL 1beta induces catecholamine release , and in turn this peptide will induce an additional increase in catecholamine release acting through the Y ( 1 ) receptor . This work suggests that NPY is involved in the regulatory loop between the immune and the adrenal system in some pathophysiological conditions where plasmatic IL 1beta increases , like in sepsis , rheumatoid arthritis , …

Molecular characterization of the acute inflammatory response to infections with gram negative versus gram positive bacteria. (2003 Sep)
molecular characterization of the acute inflammatory response to infections with gram negative versus gram positive bacteria . sepsis caused by gram negative bacteria and that caused by gram positive bacteria often manifest similar clinical features . We investigated plasma proinflammatory cytokine profiles in patients with sepsis due to gram positive and gram negative bacteria and studied the cytokine production and differential gene regulation of leukocytes stimulated ex vivo with escherichia coli lipopolysaccharide or heat killed staphylococcus aureus . concentrations of tumor necrosis factor alpha , interleukin 1 receptor antagonist ( IL 1Ra ) , IL 8 , IL 10 , IL 18 binding protein , procalcitonin , and protein C in plasma did not differ between patients with sepsis due to gram negative and gram positive bacteria . however , plasma IL 1beta , IL 6 , and IL 18 concentrations were significantly higher in patients with sepsis due to gram positive bacteria . Ex vivo stimulation of whole blood with heat killed S . aureus markedly increased IL 1beta and IL 18 levels more than E . coli lipopolysaccharide stimulation . microarray analysis revealed at least 359 cross validated probe sets ( genes ) significant at the P 0 . 001 level whose expression discriminated among gram negative organism stimulated , gram positive organism stimulated , and unstimulated whole blood leukocytes . The host inflammatory responses to gram negative and gram positive stimuli share some common response elements but also exhibit distinct patterns of cytokine appearance and leukocyte gene …

The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome. (2002 Feb)
The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome . In a prospective clinical study of 50 patients with dengue shock syndrome ( DSS ) , we investigated the association of tumor necrosis factor alpha ( TNF alpha ) , interleukin 1beta ( IL 1beta ) , IL 1 receptor antagonist ( IL 1Ra ) , and IL 6 with activation markers of coagulation ( F1 2 and TATc ) and fibrinolysis ( t PA , PAPc , and D dimer ) . We found that TNF alpha , IL 1beta and Il 1Ra , but not IL 6 , concentrations were elevated in the circulation during the early stage of infection and at discharge from hospital . TNF alpha was significantly associated with D dimer , an activation marker of fibrinolysis ( p 0 . 003 ) , but not with activation markers of coagulation . IL 1beta was significantly associated with t PA ( p 0 . 03 ) . IL 1Ra was significantly associated with F1 2 , TATc ( p 0 . 04 and p 0 . 02 , respectively ) , whereas IL 6 was significantly associated with both , activation markers of coagulation ( F1 2 ; p 0 . 03 ) and fibrinolysis ( PAPc ; p 0 . 002 ) . Our data are in line with studies in bacterial sepsis . In severe dengue virus infection the same cytokines are involved in the onset and regulation …

Roles of IL 1 and TNF in the decreased ileal muscle contractility induced by lipopolysaccharide. (1999 Jul)
roles of IL 1 and TNF in the decreased ileal muscle contractility induced by lipopolysaccharide . gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction . endotoxin lipopolysaccharide ( LPS ) impairs smooth muscle contraction , in part through inducible nitric oxide synthase ( NOS II ) and enhanced nitric oxide production . We studied the roles of tumor necrosis factor alpha ( TNF ) and interleukin 1 ( IL 1 ) in this process by using TNF binding protein ( tnfbp ) and IL 1 receptor antagonist ( IL 1ra ) . Rats were treated with tnfbp and IL 1ra , or their vehicles , 1 h before receiving LPS or saline . At 5 h after LPS , contractility was measured in strips of ileal longitudinal smooth muscle , and NOS II activity was measured in full thickness segments of ileum . LPS decreased maximum stress ( mean / SE ) from 508 / 55 ( control ) to 355 / 33 g / cm2 ( P 0 . 05 ) . pretreatment with tnfbp plus IL 1ra prevented the LPS induced decrease . separate studies of tnfbp alone or IL 1ra alone indicated that , at the doses and timing used , tnfbp was more effective . LPS also increased NOS II activity by 10 fold ( P 0 . 01 ) over control . This increase was prevented by tnfbp plus IL 1ra ( P not significant vs . control ) . We …

Bacterial lipopolysaccharide activates nuclear factor kappab through interleukin 1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. (1999 Apr)
bacterial lipopolysaccharide activates nuclear factor kappab through interleukin 1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes . bacterial lipopolysaccharide ( LPS ) mediated immune responses , including activation of monocytes , macrophages , and endothelial cells , play an important role in the pathogenesis of Gram negative bacteria induced sepsis syndrome . activation of NF kappab is thought to be required for cytokine release from LPS responsive cells , a critical step for endotoxic effects . Here we investigated the role and involvement of interleukin 1 ( IL 1 ) and tumor necrosis factor ( TNF alpha ) signal transducer molecules in LPS signaling in human dermal microvessel endothelial cells ( hdmec ) and THP 1 monocytic cells . LPS stimulation of hdmec and THP 1 cells initiated an IL 1 receptor like NF kappab signaling cascade . In transient cotransfection experiments , dominant negative mutants of the IL 1 signaling pathway , including myd88 , IRAK , irak2 , and traf6 inhibited both IL 1 and LPS induced NF kappab luciferase activity . LPS induced NF kappab activation was not inhibited by a dominant negative mutant of traf2 that is involved in TNF signaling . LPS induced activation of NF kappab responsive reporter gene was not inhibited by IL 1 receptor antagonist . TLR2 and TLR4 were expressed on the cell surface of hdmec and THP 1 cells . these findings suggest that a signal transduction molecule in the LPS receptor complex may belong to …

Pulmonary and hepatic gene expression following cecal ligation and puncture : monophosphoryl lipid A prophylaxis attenuates sepsis induced cytokine and … (1998 Aug)
pulmonary and hepatic gene expression following cecal ligation and puncture : monophosphoryl lipid A prophylaxis attenuates sepsis induced cytokine and chemokine expression and neutrophil infiltration . polymicrobial sepsis induced by cecal ligation and puncture ( CLP ) reproduces many of the pathophysiologic features of septic shock . In this study , we demonstrate that mRNA for a broad range of pro and anti inflammatory cytokine and chemokine genes are temporally regulated after CLP in the lung and liver . We also assessed whether prophylactic administration of monophosphoryl lipid A ( MPL ) , a nontoxic derivative of lipopolysaccharide ( LPS ) that induces endotoxin tolerance and attenuates the sepsis syndrome in mice after CLP , would alter tissue specific gene expression post CLP . levels of pulmonary interleukin 6 ( IL 6 ) , tumor necrosis factor alpha ( TNF alpha ) , granulocyte colony stimulating factor ( G CSF ) , IL 1 receptor antagonist ( IL 1ra ) , and IL 10 mRNA , as well as hepatic IL 1beta , IL 6 , gamma interferon ( IFN gamma ) , G CSF , inducible nitric oxide synthase , and IL 10 mRNA , were reduced in MPL pretreated mice after CLP compared to control mice . chemokine mRNA expression was also profoundly mitigated in MPL pretreated mice after CLP . specifically , levels of pulmonary and hepatic macrophage inflammatory protein 1alpha ( MIP 1alpha ) , MIP 1beta , MIP 2 , and monocyte chemoattractant protein 1 …

Interleukin 1 receptor antagonist and interleukin 6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. (1998 Nov)
interleukin 1 receptor antagonist and interleukin 6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation . background : neonatal sepsis is a common and life threatening disorder , particularly among preterm infants . early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non specific and there are no reliable early laboratory indicators . We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin 1 receptor antagonist ( IL 1ra ) , interleukin 6 ( IL 6 ) , and circulating intercellular adhesion molecule 1 ( cicam 1 ) before clinical diagnosis of sepsis . methods : In a prospective multicentre study , we monitored 182 very low birthweight infants in six intensive care units for occurrence of sepsis . during routine or clinically indicated blood sampling , an additional sample was collected for measurement of IL 1ra , IL 6 , cicam 1 , and C reactive protein ( CRP ) . infants were grouped into those with proven sepsis , no infection , or unclassified . The mean study duration was 34 days . whenever sepsis occurred , a study period of 10 days was defined : day 0 was the day of clinical diagnosis of sepsis ; days 4 to 1 were the 4 days before diagnosis ; days 1 to 5 were the 5 days after . We compared the concentrations of the immune mediators during the 10 day study …

Reduced muscle protein breakdown in septic rats following treatment with interleukin 1 receptor antagonist. (1994 Sep)
reduced muscle protein breakdown in septic rats following treatment with interleukin 1 receptor antagonist . 1 . The role of interleukin 1 ( IL 1 ) in sepsis induced muscle proteolysis was assessed by treating septic rats with recombinant IL 1 receptor antagonist ( rIL 1ra ) . 2 . In initial experiments , we tested the effectiveness of IL 1ra in preventing muscle proteolysis induced by administration of IL 1 . 3 . When normal rats were treated with rIL 1 alpha ( three intraperitoneal doses of 100 micrograms / kg body weight each over 16 hr ) , total and myofibrillar muscle protein breakdown rates , measured as release of tyrosine and 3 methylhistidine , respectively , by incubated extensor digitorum longus muscles , were significantly increased . 4 . This metabolic response to IL 1 alpha was completely abolished by rIL 1ra , administered as three intraperitoneal doses of 3 mg / kg body weight each over 16 hr . 5 . In subsequent experiments , sepsis was induced in rats by cecal ligation and puncture ( CLP ) ; non septic rats were sham operated . 6 . treatment of septic rats over 16 hr with a total dose of 25 mg / kg body weight of rIL 1ra reduced , but did not normalize , the increased muscle protein breakdown rates seen during sepsis . 7 . When the dose of rIL 1ra was more than doubled and given as a constant infusion at a …