Biological variation in the development of sepsis after surgery or trauma

Guillou, Pierre J.

doi:10.1016/0140-6736(93)92303-b

Cited by 103 publications

(43 citation statements)

References 30 publications

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“…On admission the mean age of the trauma patients ( n = 31) was 32·8 (range, 18-59), the mean ISS was 32·0 (17-59), APACHE II score of 13·5 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and mean GCS of 8·7 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). There were 25 men and six women.…”

Section: Resultsmentioning

confidence: 99%

“…1 day after the traumatic event, was evaluated by assessment of HLA-DR expression on monocytes, a parameter known to correlate with clinical outcome in diverse populations [7][8][9][10][11][12]. In addition, the proliferative capacity of T cells and cytokine production profile upon mitogenic stimulation were evaluated, because T cells are essential for a primary immune response and were reported to be functionally compromised in traumatized patients [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Boelens¹,

Fonk

Houdijk³

et al. 2004

Clinical and Experimental Immunology

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SUMMARYSevere trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) > 17]. Trauma patients ( n = 31) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-g and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Boelens¹,

Fonk

Houdijk³

et al. 2004

Clinical and Experimental Immunology

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“…Howresponse syndrome (SIRS) or sepsis (Bone, 1993) in man ever, the marked inter-species differences in the susceptibility (Guillou, 1993) means that there is no single clinical entity to be modelled. It follows, therefore, that the most useful experimental approach would simulate at least some of the characteristics of the clinical condition, and subsequently allow tion of LPS causes dysfunction in all organ systems examined (Parrillo, 1993) our particular interest is in the cardiovascular sequelae of LPS administration.…”

Section: Introductionmentioning

confidence: 99%

Cardiac and regional haemodynamics, inducible nitric oxide synthase (NOS) activity, and the effects of NOS inhibitors in conscious, endotoxaemic rats

Gardiner

Kemp

March

et al. 1995

British J Pharmacology

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1 A reproducible model of the hyperdynamic circulatory sequelae of endotoxaemia in conscious, chronically-instrumnted Long Evans rats, was achieved with a continuous infusion of lipopolysaccharide (LPS, 150 pg kg-' h'l) for 32 h. Over the first 2 h of LPS infusion, there was a transient hypotension and tachycardia, accompanied by a marked increase in renal flow and vascular conductance, although there were reductions in cardiac and stroke index. Between 4-8 h after the start of LPS infusion, there was slight hypotension and tachycardia, and a transient rise in mesenteric flow and conductance, but reductions in the hindquarters vascular bed; the hyperaemic vasodilatation in the renal vascular bed was maintained. At this stage, all cardiac haemodynamic variables and total peripheral conductance, were increased, but central venous pressure was reduced. By 24 h after the onset of LPS infusion, there was clear hypotension and tachycardia, accompanied by increases in renal and hindquarters flow and conductance, although mesenteric haemodynamic variables were not different from baseline. At this stage, cardiac and stroke index were substantially elevated, in association with marked increases in peak aortic flow, dF/dtm. and total peripheral conductance; these changes were well-maintained over the following 8 h of LPS infusion. 2 By 2 h after the start of LPS infusion, only lung inducible nitric oxide synthase (iNOS) activity was increased, but at 6 h there were significant increases in iNOS activity in lung, liver, spleen, heart and aorta (43.3±7.8, 28.8±3.3, 50.8±7.2, 3.04±0.29, 3.76±0.94 pmol min' mg -' protein, respectively). However, by 24 h after the start of LPS infusion, iNOS activity was not elevated significantly in any tissue examined, and kidney iNOS activity did not change significantly during LPS infusion. Plasma nitrite/nitrate levels were increased after 2 h infusion of LPS (from 6.07 ± 1.23 to 29.44± 7.08 pmol 1-1), and further by 6 h (228.10±29.20 pmol I-'), but were less 24 h after onset of LPS infusion (74.96±11.34 pmol I-'). Hence, the progressive hypotension, increasing cardiac function and developing hyperaemic vasodilatation in renal and hindquarters vascular beds between 8-24 h after the onset of LPS infusion, occurred when tissue iNOS activity and plasma nitrite/nitrate levels were falling.3 Pretreatment with N0-monomethyl-L-arginine (L-NMMA, 30 mg kg-' bolus, 30mg kg7' h-' infusion) 1 11 before LPS infusion did not prevent the early hypotension, but abolished the initial renal vasodilatation and the later (6-8 h) fall in mean arterial pressure (MAP), and the additional renal vasodilatation. However, under these conditions, mesenteric and hindquarters flows and conductances were substantially decreased. Similar, but less marked, effects were seen with L-NMMA pretreatment at 10 mg kg' bolus, 10 mg kg-' h-' infusion, whereas at a lower dose of 3 mg kg-' bolus, 3 mg kg' h-' infusion, L-NMMA pretreatment had little effect on responses to LPS.4 Delaying treatment with L-NMMA (10 mg kg-' bolus, 10 mg...

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“…TLRs and IL-1R share a common intracellular domain known as TLR-and IL-1R-related (TIR) 3 domain (13,16,17). Once TLR/ IL-1R is associated with ligands, the TIR domain recruits adaptor proteins, such as MyD88 (18 -20).…”

mentioning

confidence: 99%

“…Although sepsis is initiated by infection, most of the deaths are not due to infection itself, but rather multiple organ dysfunctions, including acute lung injury (2)(3)(4)(5). High circulating and tissue levels of proinflammatory cytokines, such as TNF-␣, IL-1, and IL-8, are present in septic patients and appear to contribute to organ system dysfunction in this setting (6,7).…”

mentioning

confidence: 99%

Variant IL-1 Receptor-Associated Kinase-1 Mediates Increased NF-κB Activity

Liu

Tsuruta

Gao

et al. 2007

The Journal of Immunology

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IL-1R-associated kinase (IRAK)-1 is a critical mediator of TLR/IL-1R-induced activation of the transcription factor NF-κB. We previously described that a commonly occurring IRAK-1 variant haplotype, containing amino acid changes from serine to phenylalanine at position 196 and from leucine to serine at position 532, is associated with increased activation of NF-κB in LPS-stimulated neutrophils from patients with sepsis-induced acute lung injury and also higher mortality and more severe clinical outcomes in such patients. To investigate the underlying molecular mechanisms, we examined the ability of wild-type and variant IRAK-1 to modulate NF-κB activation. We found increased NF-κB transcriptional activity and expression of NF-κB-dependent proinflammatory cytokines in IL-1β-stimulated IRAK-1-deficient cells transfected with variant IRAK-1 as compared with IRAK-1 wild type. IκB-α degradation was faster and p65 phosphorylation more prolonged after IL-1β stimulation in cells expressing the IRAK-1 variant. However, IL-1-induced activation of MAPKs and nuclear translocation of NF-κB are comparable in both IRAK-1 variant- and IRAK-1 wild-type-expressing cells. Autophosphorylation of the IRAK-1 variant is greater than that found with wild-type IRAK-1. Additionally, variant IRAK-1 has greater interaction with TNFR-associated factor 6 than does wild-type IRAK-1. The enhanced activity of variant IRAK-1 appeared to be due to the alteration at aa 532, with only minimal effects being associated with change at aa 196. These results demonstrate that variant IRAK-1 is associated with alterations in multiple intracellular events that are likely to contribute to increased NF-κB activation and inflammatory responses in individuals with this IRAK-1 haplotype.

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Biological variation in the development of sepsis after surgery or trauma

Cited by 103 publications

References 30 publications

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine

Cardiac and regional haemodynamics, inducible nitric oxide synthase (NOS) activity, and the effects of NOS inhibitors in conscious, endotoxaemic rats

Variant IL-1 Receptor-Associated Kinase-1 Mediates Increased NF-κB Activity

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