Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine aberrations may contribute to sepsis-associated mortality after trauma. We have previously documented that IL-10 (a Th-2 cytokine) is downregulated after tissue trauma, and the administration of exogenous IL-10 improved survival and anti-IL-10 antibody increased lethality in a murine injury-lethal endotox-emia model. IL-4 activates the Th-2 subset of T cells, and functions in a paracrine manner to inhibit proinflammatory cytokine synthesis. The purpose of this study was to investigate the kinetics of IL-4 production in this murine trauma-sepsis model. Mice (n = 50) were randomized to five groups: Control, Femur Fracture (FFx), FFx-lipopolysaccharide (LPS), FFx-LPS-IL10, and FFx-LPS-Anti-IL10. LPS (400 micrograms ip) was administered 4 days after FFx to induce lethal sepsis. IL-10 (0.5 microgram ip) or anti-IL-10 (100 micrograms IP) was administered at resuscitation, 30 min after LPS. IL-4 production was measured in ex vivo splenocyte culture supernatants at 24-hr intervals. Splenocyte IL-4 production was significantly upregulated in the FFx-LPS group that received anti-IL-10; maximal IL-4 production was on Day 5, with a greater than sevenfold increase compared to all other groups. A transient early rise in IL-4 production was noted in the FFx-LPS group that received exogenous IL-10; however, a subsequent rapid decline was documented. Treatment with anti-IL-10 antibody after FFx injury and septic challenge with LPS is associated with an upregulation of splenocyte IL-4 synthesis, as well as an increase in mortality in this murine model. IL-4 and IL-10 interaction postinjury may profoundly influence monocyte activation, cell-mediated immunity, and the subsequent host immune response to infection.
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PMID:Kinetics of splenocyte interleukin-4 production after injury and lethal endotoxin challenge. 907 Jan 78

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator of the acute phase response IL6 was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n = 10), adult volunteers serving as control (n = 17). Additionally, circulating cytokines were determined in cord and in maternal blood immediately after delivery (n = 27, respectively). Significant production of TNF alpha, IL8, IL10 and IL6 was observed in cord blood after lipopolysaccharide stimulation and was similar to cytokine production in adult blood. The plasma concentrations of TNF alpha were significantly higher in cord than in maternal blood, while plasma concentrations of IL10 and IL6 were significantly lower. Our results demonstrate fully developed capability of whole cord blood to synthesize pro- and anti-inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In vivo, however, higher circulating TNF alpha and lower IL10 and IL6 levels in cord blood suggest that the inflammatory stress associated with normal delivery does not induce detectable anti-inflammatory response in neonates at birth.
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PMID:The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth. 955 Nov 88

Stimulation of human blood cultures with bacterial lipopolysaccharide (LPS) shows large inter-individual variation in interleukin 10 (IL-10) secretion, which has been shown to have a genetic component of over 70%. Alleles at two microsatellite loci in the 4 kb immediately upstream of the human IL-10 transcription initiation site in 132 individuals from 56 Dutch families were defined and assigned as haplotypes. LPS-induced IL-10 secretion was measured by ELISA and related to the IL-10 promoter haplotypes present in 78 unrelated individuals obtained from these families. Analysis showed that LPS-induced IL-10 secretion from unrelated individuals varied with IL-10 promoter haplotypes (P = 0.024; Kruskal-Wallis test). Two observations were made in relation to secreted IL-10 levels and promoter haplotypes; first, those haplotypes containing the allele IL10.R3 were associated with lower IL-10 secretion than haplotypes containing any other IL10.R allele. Second, the haplotype IL10.R2/IL10.G14 was associated with highest IL-10 secretion overall, whereas the haplotype IL10.R3/IL10.G7 was associated with lowest IL-10 secretion. These data demonstrate that the ability to secrete IL-10 can vary in man according to the genetic composition of the IL-10 locus.
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PMID:Interleukin 10 secretion in relation to human IL-10 locus haplotypes. 968 3

Ex vivo production of cytokines as determined by whole blood stimulation and supernatant ELISA is partly determined by heritability. To assess the ability of this system to distinguish between high and low producers the laboratory error and individual variation were investigated. Whole blood samples from healthy volunteers were collected using endotoxin-free tubes and were incubated with 0 to 1000 ng/ml lipopolysaccharide concentrations for 4 and 24 h, and subsequently centrifuged. In the supernatants, TNF-alpha and IL10 were measured by ELISA. Coefficients of variation for the day-to-day variation in the blood sampling, transport and stimulation as well as in the whole blood stimulation per se ranged from 7.5% to 12.3%. The intra-individual variation was 15% (TNF-alpha) and 19% (IL10) in contrast to the inter-individual variation of, on average, 35%. No interchanging of ranks between high and low producers was observed after repeating the whole blood stimulation on distinct days. The whole blood stimulation system is able to distinguish high and low producers of TNF-alpha and IL10.
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PMID:Determination of tumour necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation. 981 23

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of malignant plasma cells in the bone marrow. It is unclear whether genetic background could have an etiological impact on MM or influence the course of the disease. Interleukin-10 (IL-10) has been implicated in the growth and differentiation of normal B cells, and has also been shown to enhance the proliferation of MM cells. To address the putative involvement of IL-10 genetic variation in MM, we analyzed previously defined loci for bi-allelic polymorphism at position -1082 and two microsatellite loci (IL10.G and IL10.R) in the IL-10 promoter region. Seventy-three patients with MM, 27 with monoclonal gammopathy of undetermined significance, and 109 ethnically matched individuals as controls were included in the study. Significantly increased frequencies of the IL10.G genotype 136/136 and the IL10.R genotype 112/114, in addition to a decreased frequency of the IL10.R genotype 114/116, were found among the MM patients. Increased production of IL-10 was detected in the supernatants of lipopolysaccharide-stimulated peripheral blood mononuclear cells from MM patients who were homozygotes (136/136) and heterozygotes (136/non-136) for the IL10.G allele 136, as compared with the other IL10.G genotype carriers (non-136/non-136). These results suggest that the genetic variation in the IL-10 promoter region may play a role in the development of MM.
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PMID:Interleukin-10 gene promoter polymorphisms in multiple myeloma. 1130 52

The atrial natriuretic peptide (ANP), a member of the natriuretic peptide family, is a cardiovascular hormone which possesses well defined natriuretic, diuretic, and vasodilating properties. Most of the biological effects of ANP aremediated through its guanylyl cyclase coupled A receptor. Because ANP and its receptors have been shown to be expressed and differentially regulated in the immune system, it has been suggested that ANP has an immunomodulatory potency. Much investigation of the effects of ANP on the activation of macrophages has been carried out. ANP was shown to inhibit the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) in macrophages in an autocrine fashion. ANP in this context was shown to reduce significantly the activation of NF-kappaB and to destabilise iNOS mRNA. ANP, furthermore, can significantly reduce the LPS-induced secretion of tumour necrosis factor alpha (TNFalpha) in macrophages. The relevance of these findings on a regulatory role for ANP on TNFalpha in humans was shown by the fact that ANP significantly reduces the release of TNFalpha in whole human blood. It was furthermore shown to attenuate the release of interleukin 1beta (IL1beta). Interestingly, ANP did not affect the secretion of the anti-inflammatory cytokines IL10 and IL1 receptor antagonist (IL1ra). In summary, ANP was shown to reduce the secretion of inflammatory mediators in macrophages. Therefore, this cardiovascular hormone may possess anti-inflammatory potential.
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PMID:The atrial natriuretic peptide regulates the production of inflammatory mediators in macrophages. 1189 Jun 59

IL-10 inhibits the production of many pro-inflammatory cytokines. Polymorphisms in the IL10 gene promoter at positions -1082G-->A, -819C-->T and -592C-->A occur as three haplotypes, ATA, GCC and ACC. These influence several infectious and inflammatory diseases including community-acquired pneumonia, where a role for IL-10 is suggested by fluctuations in plasma levels of the cytokine. However, the effects of the haplotypes on IL-10 production are unclear. We stimulated peripheral blood mononuclear cells (PBMC) from at least five individuals homozygous for each of the three haplotypes with lipopolysaccharide (LPS, 10 microg/ml) or heat-killed Streptococcus pneumoniae (10(7)cfu/ml) and measured IL-10 mRNA by RT-PCR. Following S. pneumoniae stimulation, PBMC with the ATA haplotype had higher IL-10 mRNA levels than those with the GCC haplotype at 4 h (independent t-test; P=0.024), or the ACC haplotype at 4 h ( P<0.0001) and 8 h ( P=0.007). Following LPS stimulation, IL-10 mRNA levels were not significantly influenced by the IL10 haplotype, but similar trends were observed, consistent with the variable outcome of published studies. The results suggest that the -819 and/or -592 alleles affect transcription.
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PMID:Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. 1460 76

Adiponectin, an adipocyte-derived hormone, attenuates the production of TNFalpha by activated human macrophages. In the present study, we used porcine blood-derived macrophages to test the hypothesis that the anti-inflammatory action of adiponectin includes suppression of IL6 and an induction of IL10. Adiponectin suppressed both TNFalpha and IL6 production in macrophages activated with lipopolysaccharide (P<0.01). In contrast, adiponectin increased IL10 expression (P<0.05) and augmented (P<0.05) the induction of this cytokine by lipopolysaccharide (LPS). Mechanistically, the attenuation of proinflammatory cytokine production by adiponectin was associated with an attenuation of the translocation of NFkappaB to the nucleus. Either adiponectin or inhibition of ERK1/2 with U0126 diminished the induction of IL6 by LPS (P<0.05), but the combination of adiponectin and the inhibitor did not further reduce IL6 production. In contrast, the inhibitory actions of adiponectin and a p38 MAPK inhibitor (SB203580) were additive (P<0.05). These data indicate that the anti-inflammatory actions of adiponectin include suppression of IL6 and induction of IL10. In addition, we provide evidence that some of the anti-inflammatory actions of adiponectin are mediated in part by suppression of NFkappaB signaling and ERK1/2 activity.
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PMID:Adiponectin differentially regulates cytokines in porcine macrophages. 1503 90

Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5'-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo- and genotypes are identified present at differing frequencies in three geographically separated populations. Their influence on IL-10 expression have been assessed in vitro after stimulation of leukocytes with lipopolysaccharide (LPS), dibutyryl-cAMP or following immortalisation with Epstein-Barr virus (lymphoblastoid cell line (LCL)). Interindividual differences of IL-10 production were found to be related to single-nucleotide polymorphisms (SNP) haplotype -6752/-6208 in LCLs (P<0.02), and for haplotypes comprising SNPs -6752/-6208/-3538 after LPS stimulation (P<0.03). Carriers of the IL10.G microsatellite with 22, 24 or 26 dinucleotide repeats linked with the -1087G SNP, exhibited the highest levels of IL-10 expression. Contrasting IL-10 secretion patterns were found for IL10.R microsatellite alleles characterised by 15 dinucleotide repeats: after LPS stimulation this allele was associated with high IL-10 production (P<0.007), but with low IL-10 levels in LCLs (P< 0.038). Thus, the effects of mosaics of genetic elements in the PIL-10 on the capacity of leukocytes to produce IL-10 depend on the agent inducing IL-10 expression.
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PMID:Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. 1511 66

The objective of this study was to quantify the ability of sublethal concentrations of several gold compounds to differentially modulate the monocytic secretion of key cytokines that are important in the etiology of rheumatic diseases. Human THP1 monocytic cells were exposed to the anti-rheumatic drugs auranofin (AF), gold sodium thiomalate (GSTM) or HAuCl4 (Au(III)) for 24-72 h. Succinate dehydrogenase (SDH) activity of the monocytes was used to determine sublethal concentrations. Monocytes were then exposed to sublethal concentrations of gold compounds for 72 h, and the activator lipopolysaccharide (LPS) was added (or not) to cultures for the last 6h. The secretion of IL6, IL8, IL10, and TNFalpha were measured in cell supernatants using ELISA. Cytokine secretion was compared among concentrations and gold compounds. SDH experiments established a sublethal concentration range of 0-75 microM for GSTM and Au(III) and 0-0.5 microM for AF. In cytokine experiments, none of the compounds alone activated secretion of any of the cytokines, but all differentially (50-440%, p<0.05) increased LPS-induced secretion of IL6 and IL8 over TNFalpha and IL10. In conclusion, sublethal concentrations of AF, GSTM, and Au(III) all may differentially modulate activation of monocytic cells, and this differential modulation may be important in the mechanisms of action of these compounds.
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PMID:Anti-rheumatic gold compounds as sublethal modulators of monocytic LPS-induced cytokine secretion. 1571 43


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