| 1. |
- Aalto, K, et al.
(författare)
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Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity
- 2002
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Ingår i: Cytokine. - : ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD. - 1043-4666 .- 1096-0023. ; 20:3, s. 136-139
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor (NGF) is a neurotrophic factor, which is expressed both in the nervous system and in peripheral organs. NGF is also present in mast cells, and in B- and T-lymphocytes, and may play a role in the immune cell development and differentiation. Various cytokines have been shown to affect NGF expression, and NGF is elevated in inflammation and in some autoimmune diseases. Here we have studied NGF concentrations in serum of pediatric patients with systemic lupus erythematosus (SLE) using a two-site enzyme-linked immunosorbent assay (ELISA). We have further correlated the levels of NGF to the inflammatory state of the disease. The mean value of serum NGF in SLE patients was significantly increased compared with controls (3346 vs 627 pg/ml). There was a correlation between the activity of SLE and the levels of NGF. The results show that NGF is elevated in childhood SLE and that the levels are correlated with disease activity. The present results suggest that NGF may play a role in the pathogenesis of SLE and may have a prognostic value in evaluating the course of the disease and in outlining the medication. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 2. |
- Alm, Ann-Sophie, et al.
(författare)
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Varying susceptibility of pulmonary cytokine production to lipopolysaccharide in mice.
- 2010
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 49, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The lipopolysaccharide (LPS)-induced acute lung injury (ALI) model has been widely applied for pathophysiological and pharmacological research. The aim of present study is to understand the variation of acute pulmonary inflammation between mouse strains. Methods: The present study investigated the susceptibility of acute production of inflammatory mediators, e.g. cytokines, chemokines and others, to LPS in C57BL/6J, Balb/cJ, DBA/1J, CD-1, NMRI, DBA/2J, A/J, and C3H/HeN mice. Results: The susceptibility to intra-tracheal challenge with LPS varied between measured variables, durations and strains. General lung hyper-reactive susceptibility to LPS-induced pulmonary production of 6-8 inflammatory mediators followed the order NMRI, Balb/cJ, C3H/HeN, A/J, C57BL/6J, DBA/1J, DBA/2J and CD-1 mice at 4h, and A/J, C3H/HeN, CD-1, NMRI, C57BL/6J, Balb/cJ, DBA/2J and DBA/1J mice at 24h. Conclusions: Our data provide information for scientists to consider the proper strain of mice for the measurement of specific inflammatory mediators and to select sensitive or resistant mouse strains for understanding genetic variation in the pathogenesis and for the screening of target-oriented drug development.
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| 3. |
- Almqvist, Sofia, 1980, et al.
(författare)
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Amelogenins modulate cytokine expression in LPS-challenged cultured human macrophages.
- 2012
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 58:2, s. 274-9
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Tidskriftsartikel (refereegranskat)abstract
- Amelogenins are enamel matrix proteins with a proven ability to restore tissues in patients with advanced periodontitis and chronic skin wounds. To explore the mechanisms of action of amelogenins in wound inflammation, the in vitro effect on the expression of selected cell mediators involved in inflammation and tissue repair from human monocyte-derived macrophages was studied. Macrophages were treated with amelogenins in serum-enriched medium with simultaneous lipopolysaccharide (LPS) stimulation, for 6, 24 and 72 h, and the conditioned culture medium was analysed for 28 different cytokines. Amelogenin treatment directed the LPS-induced release of both pro- and anti-inflammatory cytokines towards an alternatively activated macrophage phenotype. This change in activation was also demonstrated by the amelogenin-induced secretion of alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known as CCL18; p<0.001), a well-documented marker of alternative activation. Amelogenins were also shown significantly to increase the macrophage expression of vascular endothelial growth factor and, to a lesser but significant extent, insulin-like growth factor-1 after 24h of culture. The results of the present in vitro study show that monocyte-derived macrophages stimulated by inflammatory agonist LPS respond to the treatment with amelogenins by reducing the pro-inflammatory activity and increasing the expression of tissue repair mediators.
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| 4. |
- Andersson, Karolina, et al.
(författare)
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Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation factor 4E (eIF4E) phosphorylation in mouse macrophages.
- 2006
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 33:1, s. 52-57
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Tidskriftsartikel (refereegranskat)abstract
- Resident mouse macrophages secrete Tumor necrosis factor α (TNFα) upon challenge with LPS. The production of TNFα is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFα, through the downstream kinase Mnk1. TNFα production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly, the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFα production, arguing against a direct/immediate role for this kinase. On the basis of the present and previous results we propose that ARE-containing TNFα mRNA requires phosphorylation of eIF4E for initiation of translation.
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| 5. |
- Bahnasawy, Salma M., et al.
(författare)
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Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli
- 2023
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 169
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Tidskriftsartikel (refereegranskat)abstract
- Background: Describing the kinetics of cytokines involved as biomarkers of sepsis progression could help to optimise interventions in septic patients. This work aimed to quantitively characterise the cytokine kinetics upon exposure to live E. coli by developing an in silico model, and to explore predicted cytokine kinetics at different bacterial exposure scenarios.Methods: Data from published in vivo studies using a porcine sepsis model were analysed. A model describing the time courses of bacterial dynamics, endotoxin (ETX) release, and the kinetics of TNF and IL-6 was developed. The model structure was extended from a published model that quantifies the ETX-cytokines relationship. An external model evaluation was conducted by applying the model to literature data. Model simulations were performed to explore the sensitivity of the host response towards differences in the input rate of bacteria, while keeping the total bacterial burden constant.Results: The analysis included 645 observations from 30 animals. The blood bacterial count was well described by a one-compartment model with linear elimination. A scaling factor was estimated to quantify the ETX release by bacteria. The model successfully described the profiles of TNF, and IL-6 without a need to modify the ETXcytokines model structure. The kinetics of TNF, and IL-6 in the external datasets were well predicted. According to the simulations, the ETX tolerance development results in that low initial input rates of bacteria trigger the lowest cytokine release.Conclusion: The model quantitively described and predicted the cytokine kinetics triggered by E. coli exposure. The host response was found to be sensitive to the bacterial exposure rate given the same total bacterial burden.
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| 6. |
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| 7. |
- Barstad, Bjorn, et al.
(författare)
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Cerebrospinal fluid cytokines and chemokines in children with Lyme neuroborreliosis; pattern and diagnostic utility
- 2020
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Ingår i: Cytokine. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1043-4666 .- 1096-0023. ; 130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lyme neuroborreliosis (LNB) is characterized by cerebrospinal fluid (CSF) inflammation with several cytokines/chemokines and B-lymphocytes. Clinically, LNB in children may be difficult to discriminate from non-Lyme aseptic meningitis (NLAM). We aimed to identify CSF cytokine/chemokine patterns in children with LNB, NLAM and controls and elucidate the diagnostic value of these cytokines/chemokines alone or in combination to discriminate between LNB and NLAM. Methods: Children with symptoms suggestive of LNB were included prospectively and categorized as LNB, NLAM or controls (no pleocytosis). Cytokines/chemokines in CSF were measured by multiplex bead assays and levels were compared between the three groups by nonparametric statistical tests. Previous results from the same children on the established biomarker, CXCL13, were included in the statistical analyses. The diagnostic properties of cytokines/chemokines to discriminate between LNB and NLAM were determined by receiver operating characteristic curve analyses with estimates of area under curve (AUC). To explore diagnostic properties of combinations of cytokines/chemokines, prediction models based on logistic regression were used. Results: We included 195 children with LNB (n = 77), NLAM (n = 12) and controls (n = 106). Children with LNB had higher CSF levels of CCL19, CCL22 and CXCL13 compared to NLAM and controls, whereas INF. was higher in NLAM than in LNB and controls. CXCL13 was the superior single cytokine/chemokine to discriminate LNB from NLAM (AUC 0.978). The combination CXCL13/CCL19 (AUC 0.992) may possibly improve the specificity for LNB, especially for children with moderate CXCL13 levels. Conclusions: The intrathecal immune reaction in LNB is characterized by B cell associated chemokines. Whether the combination CXCL13/CCL19 further improves discrimination between LNB and NLAM beyond the diagnostic improvements by CXCL13 alone needs to be tested in new studies.
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| 8. |
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| 9. |
- Bay-Richter, Cecilie, et al.
(författare)
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Aldosterone synergizes with peripheral inflammation to induce brain IL-1β expression and depressive-like effects.
- 2012
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 60:3, s. 749-754
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings have shown that the physiological functions of the hormone aldosterone go far beyond its well-known role in blood-pressure regulation and salt/water homeostasis. Aldosterone is for example involved in the regulation of inflammation, and also binds directly to mineralocorticoid receptors in specific brain regions. Interestingly, depressive symptoms appear to correlate with alterations of the aldosterone system but the underlying mechanisms have not been elucidated. In this study aldosterone (2μg/100g body weight/day) was continuously administered via osmotic minipumps for 5days. Lipopolysaccharide (LPS) was administered once a day for 5days in a dose of 1mg/kg ip. The rats were tested for depressive-like behavior 24h after the last LPS injection. Protein levels of cytokines were measured in serum and cerebrospinal fluid (CSF). mRNA expression of interleukin (IL)-1β and IL-6 in the prefrontal cortex (PFC) was analyzed using reverse transcriptase qPCR. We found that aldosterone treatment increased LPS-induced IL-1β mRNA expression in the PFC and CSF. Moreover, there was a positive correlation between IL-1β in CSF and depressive-like behaviors. These findings suggest that IL-1β is affected by the renin-aldosterone-angiotensin system (RAAS) activity and connected to symptoms of depression.
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| 10. |
- Belibasakis, Georgios N., et al.
(författare)
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Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes
- 2012
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Ingår i: Cytokine. - : Elsevier. - 1043-4666 .- 1096-0023. ; 59:1, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1β and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.
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