Immunopathogenesis of schistosomiasis. (2004 Sep)
immunopathogenesis of schistosomiasis . In schistosomiasis mansoni , the chronic egg induced granulomatous response in the liver and intestines may eventually cause extensive tissue scarring and development of portal hypertension . indeed , much of the morbidity and mortality associated with this disease is directly attributable to the deposition of connective tissue elements in affected tissues . elucidating the mechanisms that regulate the severity of schistosomiasis has been a major research objective over the past several years . research conducted with DNA microarrays as well as investigations with a variety of gene knock out mice have been particularly helpful in achieving this goal . A notable accomplishment in the past few years was the identification of interleukin 13 ( IL 13 ) and the IL 13 receptor complex as central regulators of disease progression in schistosomiasis . liver fibrogenesis is severely decreased in infected IL 13 deficient mice as well as in wildtype animals treated with IL 13 antagonists . In contrast , IL 13 effector function increases dramatically in IL 13 receptor alpha2 ( IL 13ralpha2 ) deficient mice . these mice develop severe hepatic fibrosis , fail to downregulate granuloma formation in the chronic phase of S . mansoni infection , and succumb to the disease at an accelerated rate ; thus , identifying the decoy IL 13 receptor as a critical life sustaining off switch for tissue damaging egg induced inflammation .

Induction of allergic inflammation by interleukin 18 in experimental animal models. (2004 Nov)
induction of allergic inflammation by interleukin 18 in experimental animal models . interleukin 18 ( IL 18 ) has been regarded as a proinflammatory cytokine because of its potent interferon gamma inducing activity . however , mutant mice that release excess amounts of IL 18 spontaneously develop pruritic chronic dermatitis like atopic dermatitis ( AD ) , suggesting the importance of IL 18 for the development of AD . intriguingly , depletion of il 18 but not stat6 , an essential transcriptional factor for IL 4 signaling , rescues the mice from AD , indicating IL 18 dependent , T helper 2 ( Th2 ) cell independent AD . This type of AD is classified as innate type allergy in contrast to Th2 cell dependent ordinary allergy . consistent with the previous studies , mice transferred with antigen specific Th1 cells exhibit no airway hyperresponsiveness and respiratory eosinophilic inflammation after challenge with antigen alone . however , they suffer from asthma upon challenge with antigen plus IL 18 , with comparable levels of both the alterations as in those transferred with Th2 cells following challenge with antigen . The former type of asthma is categorized as Th1 associated allergy . therefore , it is definitely necessary to evaluate whether individual allergic disorders involve either of these IL 18 mediated pathways or a Th2 mediated one .

Opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease. (2004 Nov)
opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease . interleukin ( IL ) 13 is a key inducer of several type 2 cytokine dependent pathologies . It regulates inflammation , mucus production , tissue remodeling , and fibrosis . consequently , it has become an important therapeutic target for a number of debilitating illnesses , including asthma , idiopathic pulmonary fibrosis , ulcerative colitis , as well as several other diseases in which IL 13 is believed to be overproduced . In the murine model of schistosomiasis , IL 13 has emerged as a central mediator of chronic infection induced liver pathology . although IL 4 , IL 5 , IL 10 , and IL 13 each regulate distinct aspects of the granulomatous inflammatory response , IL 13 was identified as the primary mediator of liver fibrosis . Thus , elucidating the mechanisms that regulate the production and function of IL 13 has become an intensive area of research . IL 13 signaling is mediated by the type 2 IL 4 receptor , which consists of the IL 4R alpha and IL 13R alpha 1 chains . however , another IL 13 binding chain , IL 13R alpha 2 , appears to strongly inhibit the activity of IL 13 . animals deficient in IL 13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection . They also develop severe IL 13 dependent fibrosis and portal hypertension and quickly succumb …

Interleukin 17A mRNA and protein expression within cells from the human bronchoalveolar space after exposure to organic dust. (2005 Jun)
interleukin 17A mRNA and protein expression within cells from the human bronchoalveolar space after exposure to organic dust . background : In mice , the cytokine interleukin ( IL ) 17A causes a local accumulation of neutrophils within the bronchoalveolar space . IL 17A may thereby also contribute to an increased local proteolytic burden . In the current study , we determined whether mRNA for IL 17A is elevated and protein expression of IL 17A occurs locally in inflammatory cells within the human bronchoalveolar space during severe inflammation caused by organic dust . We also assessed the expression of the elastinolytic protease MMP 9 in this airway compartment . methods : Six healthy , non smoking human volunteers were exposed to organic dust in a swine confinement , a potent stimulus of neutrophil accumulation within the human bronchoalveolar space . bronchoalveolar lavage ( BAL ) fluid was harvested 2 weeks before and 24 hours after the exposure and total and differential counts were conducted for inflammatory BAL cells . messenger RNA for IL 17A was measured using reverse transcript polymerase chain reaction enzyme linked immunoassay ( RT PCR elisa ) . intracellular immunoreactivity ( IR ) for IL 17A and MMP 9 , respectively , was determined in BAL cells . results : The exposure to organic dust caused more than a forty fold increase of mRNA for IL 17A in BAL cells . IL 17A immunoreactivity was detected mainly in BAL lymphocytes , and the number of these IL …

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 …

Interleukin 6 production by human neonatal monocytes stimulated by type III group B streptococci. (1996 Sep)
interleukin 6 production by human neonatal monocytes stimulated by type III group B streptococci . The subcellular components of type III group B streptococci ( GBS ) that contribute to the host inflammatory response were determined by measuring production of the proinflammatory cytokine interleukin ( IL ) 6 by cord blood monocytes . monocytes were stimulated with encapsulated ( COH1 ) or unencapsulated ( COH1 13 ) whole type III GBS or with purified GBS components , including type III capsular polysaccharide ( III PS ) , group B antigen ( GB Ag ) , lipoteichoic acid ( LTA ) , or escherichia coli lipopolysaccharide . monocytes exposed to COH1 and COH1 13 released similar amounts of IL 6 . GBS III PS , GB Ag , and LTA each induced IL 6 . however , IL 6 release by monocytes was significantly greater after stimulation by GB Ag than by III PS or LTA ( P . 05 ) . Sera from 16 neonates with systemic GBS disease had IL 6 levels of 8 pg / mL to 4 . 28 ng / mL . GB Ag is a potent inducer of IL 6 and may play an important role in tissue inflammation during GBS infection .

Unidirectional heterologous receptor desensitization between both the fMLP and C5a receptor and the IL 8 receptor. (1996 Sep)
unidirectional heterologous receptor desensitization between both the fMLP and C5a receptor and the IL 8 receptor . during inflammation neutrophils receive multiple signals that are integrated , allowing a single modified response . One mechanism for this discrimination is receptor desensitization , a process whereby ligand receptor binding is disassociated from cell activation . We examined the effect of heterologous receptor desensitization on neutrophil chemotaxis , calcium mobilization , and arachidonic acid production , using interleukin 8 ( IL 8 ) , C5a , and N formyl methionyl leucyl phenylalanine ( fMLP ) . We observed reciprocal inhibition with respect to chemotaxis . We demonstrated that homologous desensitization , with respect to the mobilization of intracellular calcium stores , lasted approximately 15 min . heterologous desensitization between the fMLP receptor and the C5a receptor was reciprocal ; either stimulant would diminish the cells response to stimulation by the other for approximately 3 5 min . however , we observed a unidirectional heterologous desensitization of the IL 8 receptor by both the fMLP and the C5a receptor . This unidirectional heterologous desensitization was observed with respect to both calcium mobilization and arachidonic acid production ( i . e . , prestimulation of the IL 8 receptor had no effect on subsequent stimulation by either fMLP or C5a ) .

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 , …

Signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4. (2004 Nov)
signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4 . produced in response to a variety of pathogenic organisms , interleukin ( IL ) 12 and IL 23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses . these dimeric cytokines share a subunit , designated p40 , and bind to a common receptor chain , IL 12R beta 1 . The receptor for IL 12 is composed of IL 12R beta 1 and IL 12R beta 2 , whereas IL 23 binds to a receptor composed of IL 12R beta 1 and IL 23R . Both cytokines activate the janus kinases Tyk2 and Jak2 , the transcription factor signal transducer and activator of transcription 4 ( stat4 ) , as well as other stats . A major action of IL 12 is to promote the differentiation of naive CD4 T cells into T helper ( Th ) 1 cells , which produce interferon ( IFN ) gamma , and deficiency of IL 12 , IL 12R subunits or stat4 is similar in many respects . In contrast , IL 23 promotes end stage inflammation . targeting IL 12 , IL 23 , and their downstream signaling elements would therefore be logical strategies for the treatment of immune mediated diseases .

Increased expression of plasminogen activator inhibitor 1 by mediators of the acute phase response : a potential progenitor of vasculopathy … (2003 Nov)
increased expression of plasminogen activator inhibitor 1 by mediators of the acute phase response : a potential progenitor of vasculopathy in hypertensives . hypertension is an important risk factor for coronary atherosclerosis , which is accelerated by inflammation and diminished fibrinolysis . We have previously shown that levels of plasminogen activator inhibitor 1 ( PAI 1 ) , the major physiologic inhibitor of fibrinolysis , are increased with atherogenic metabolic derangement . because the liver is one of the major sources of circulating PAI 1 , we here examined the effects of two proinflammatory cytokines , interleukin ( IL ) 1beta , and IL 6 , on PAI 1 production in a human hepatoma cell line , hepg2 . IL 1beta ( 1 ng / ml ) and IL 6 ( 1 ng / ml ) increased the accumulation of PAI 1 in the conditioned media over 24 h ( IL 1beta : 2 . 1 / 0 . 2 ( mean / SD ) fold over the control ; IL 6 : 1 . 4 / 0 . 2 fold ; western blot , p 0 . 05 ) . The increase in PAI 1 protein accumulation correlated with the increased expression of PAI 1 mRNA ( northern blot ) . An HMG CoA reductase inhibitor ( mevastatin , 10 micromol / l ) attenuated the PAI 1 production induced by IL 1beta and IL 6 . The plasma PAI 1 activity level was higher in hypertensives than in …

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 .

Pathogenic role of interleukin 6 in the development of sepsis. (2003 May)
pathogenic role of interleukin 6 in the development of sepsis . Part II : significance of anti interleukin 6 and anti soluble interleukin 6 receptor alpha antibodies in a standardized murine contact burn model . objective : The in vivo effects of anti interleukin 6 ( anti IL 6 ) and anti interleukin 6 alpha receptor ( anti IL 6R ) monoclonal antibodies on immune response and survival rate of a burn with subsequent infection were assessed . subjects : Ten week old C 57 BL / 6J mice received a standardized contact burn ; 48 hrs later endotoxin ( LPS ) was injected intraperitoneally to induce systemic inflammation . Ten different groups were studied . groups I IV sustained a burn and / or a LPS stimulus but did not receive any anti cytokines and served as controls . treatment groups V X sustained the same injuries but also received anti IL 6 and anti IL 6R intravenously either before or after the LPS stimulus . In a further part of the study , a lethal dose of LPS was injected ( LPS LD ( 100 ) group ) followed by an injection of anti IL 6 antibody and / or anti IL 6R antibody . measurements : serum concentrations of IL 6 , tumor necrosis factor ( TNF ) alpha , interferon ( IFN ) gamma , and white blood cell and platelet counts were determined , and the survival rate over a 2 wk period was assessed …

Expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies. (2004 Mar)
expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies . interleukin 12 ( IL 12 ) is a key heterodimeric cytokine produced by a variety of antigen presenting cells , including dendritic cells , macrophages , and B cells . It displays a potent array of biological activities affecting natural killer ( NK ) and T cells . these activities include promotion of cell mediated or type 1 T helper cell responses ( Th1 ) . Due to that property , IL 12 has been employed in cancer immunotherapy , in mouse models of infectious diseases and in airway inflammation , and it may also have utility as a vaccine adjuvant . transgenic plants are being used in many laboratories around the world for the production of therapeutically valuable proteins and as vehicles for oral vaccines . Here we present the expression of a single chain human interleukin 12 in transgenic tobacco plants . The biological activity of plant produced IL 12 was determined by interferon gamma ( IFN gamma ) production by natural killer ( NK ) cells , and the level of production was comparable to that obtained with commercially available recombinant IL 12 . The potential use of this recombinant protein is discussed .

Cytokines and the chronic inflammation of rheumatic disease. (1988 Mar)
cytokines and the chronic inflammation of rheumatic disease . III . deficient interleukin 2 production in rheumatoid arthritis is not due to suppressor mechanisms . despite the evidence for activated T cells in the joint in rheumatoid arthritis ( RA ) , there is evidence of deficient lymphocyte proliferation to a variety of stimulants . We investigated the production of interleukin 2 ( IL 2 ) after phytohemagglutinin ( PHA ) stimulation . We show that in the peripheral blood IL 2 production was similar in RA and controls ( 3 . 7 vs 3 . 0 U / ml , respectively ) . however , blood lymphocytes from patients with joint effusions produced significantly less IL 2 than from patients without effusions ( 1 . 8 vs 5 . 7 U / ml , respectively ) . The amount of IL 2 produced by synovial fluids ( SF ) cells was significantly less than that produced by the corresponding blood cells ( 1 . 0 vs 1 . 6 U / ml ) . further experiments revealed that the decreased IL 2 production was not due to its removal by IL 2 receptor positive cells in the SF and cell mixing experiments did not reveal any suppressor influences .

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 …

Involvement of IL 6 , apart from its role in immunity , in mediating a chronic response during experimental arthritis. (2000 Dec)
involvement of IL 6 , apart from its role in immunity , in mediating a chronic response during experimental arthritis . interleukin 6 ( IL 6 ) is highly produced during arthritis but its exact function is still unknown . In this study we examined if IL 6 , apart from its role in immunity , was involved in the local inflammatory response in experimental arthritis . IL 6 deficient ( IL 6 ( / ) ) and wild type mice were first compared in the antigen induced arthritis model . IL 6 deficiency resulted in a mild , transient inflammation whereas wild type mice developed a chronic , destructive synovitis . Wild type mice immunized with one tenth of the normal antigen dose still developed chronic arthritis despite low antibody levels , excluding reduced humoral immunity in IL 6 ( / ) mice as a crucial phenomenon . In addition , passive immune complex induced arthritis did not differ between wild type and IL 6 ( / ) mice . another option is reduced levels of Th1 cells in IL 6 ( / ) mice . however , transfer of antigen specific wild type lymph node cells to IL 6 ( / ) mice enhanced acute joint inflammation and increased cartilage damage but still could not sustain chronic inflammation , suggesting involvement of nonimmune elements of IL 6 activity in chronicity . In line with this , nonimmunologically mediated zymosan induced arthritis developed similarly in the first week , …

Pharmacogenomics of neuroimmune interactions in human psychiatric disorders. (2007 Sep)
pharmacogenomics of neuroimmune interactions in human psychiatric disorders . there is bidirectional communication between the brain and the immune system . overproduction of interleukin 1beta ( IL 1beta ) leads to systemic inflammatory response syndrome ( SIRS ) . The crucial role of IL 1beta in inflammation has been highlighted by studies performed in caspase 1 knockout mice ( casp1 ( / ) ) , transgenic mice that lack mature IL 1beta and survive lethal doses of lypopolysaccharide ( LPS ) . We have previously shown that IL 1beta , its receptor IL 1 receptor I ( IL 1RI ) and caspase 1 are expressed within the brain . moreover , we documented that peripherally injected LPS triggers a specific spatiotemporal pattern of expression of IL 1beta mRNA within the brain , suggesting that IL 1beta could be a major regulator of the central inflammatory cascade . therefore , we studied brain transcriptional patterns that occur during LPS induced SIRS in wild type and casp1 ( / ) mice . We showed patterns of gene expression in wild type and casp1 ( / ) mice that included differential expression of several genes , such as those for cytokines , chemokines , nitric oxide synthase 2 and cyclo oygenase 2 . A key component of the neuroimmune endocrine axis that is increased by IL 1beta is corticotrophin releasing hormone ( CRH ) . We found increased response to antidepressants in patients homozygous for the GAG haplotype of CRH receptor 1 . …