Institute for Inflammation Research

Denmark

Institute for Inflammation Research

Denmark
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Muller K.,Institute for Inflammation Research | Muller K.,Copenhagen University
Bone Marrow Transplantation | Year: 2017

Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) play key roles in initiating innate and adaptive immune responses. Based mainly on animal studies there is growing evidence to suggest that TLRs are involved in the development of chemotherapy-induced mucositis and in the propagation of graft versus host reactions as well as graft versus tumor effects in allogeneic hematopoietic stem cell transplantation (HSCT). In this review we discuss these findings along with the emerging, although still preliminary, clinical evidence, that points to a role of PRRs in determining the outcome of HSCT and new therapeutic perspectives that may be related to this development. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


Kielsen K.,Institute for Inflammation Research | Kielsen K.,Copenhagen University | Shamim Z.,Institute for Inflammation Research | Shamim Z.,Copenhagen University | And 7 more authors.
Journal of Immunotoxicology | Year: 2016

Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, 12 healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results suggested that cellular mechanisms right after antigen exposure should be investigated more closely to identify possible mechanisms of immunosuppression from PFAS. © 2015 Informa UK Limited trading as Taylor & Francis Group.


PubMed | Institute for Inflammation Research
Type: | Journal: Bone marrow transplantation | Year: 2016

Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) play key roles in initiating innate and adaptive immune responses. Based mainly on animal studies there is growing evidence to suggest that TLRs are involved in the development of chemotherapy-induced mucositis and in the propagation of graft versus host reactions as well as graft versus tumor effects in allogeneic hematopoietic stem cell transplantation (HSCT). In this review we discuss these findings along with the emerging, although still preliminary, clinical evidence, that points to a role of PRRs in determining the outcome of HSCT and new therapeutic perspectives that may be related to this development.Bone Marrow Transplantation advance online publication, 12 December 2016; doi:10.1038/bmt.2016.263.


Vitfell-Pedersen J.,Royal Marsden Hospital | Jorgensen M.H.,Institute for Inflammation Research | Muller K.,Institute for Inflammation Research | Heilmann C.,Institute for Inflammation Research
Journal of Pediatric Gastroenterology and Nutrition | Year: 2012

Objectives: Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early treatment strategies on the course of disease. Methods: A population-based cohort of patients from January 1993 to September 2009 was identified prospectively, and the patient data were collected by a retrospective examination of the files. Results: Twenty-nine patients had type 1 AIH, 2 had type 2, and 2 could not be categorised. Among the 33 children, 16 (48.5%) were girls and 17 (51.5%) were boys. Twenty-three (69.7%) of the patients had symptoms at presentation indistinguishable from acute viral hepatitis, but in 16 (69.6%) of those the liver biopsy showed cirrhosis. Twenty (60.6%) patients were treated with prednisolone and azathioprine at the time of remission, whereas 8 (24.2%) were treated with prednisolone. One (3%) patient did not experience remission during the observation period. Conclusions:: The patients in our study appeared similar to previously published cohorts, although a female predominance was not observed. Our data suggest that early treatment including both prednisolone and azathioprine could be more effective than prednisolone alone, even if randomised controlled paediatric studies comparing these 2 different treatment regimens are needed. Copyright © 2012 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.


Belstrom D.,Copenhagen University | Fiehn N.-E.,Copenhagen University | Nielsen C.H.,Institute for Inflammation Research | Holmstrup P.,Copenhagen University | And 5 more authors.
Caries Research | Year: 2014

The aim of this study was to learn whether presence of caries in an adult population was associated with a salivary bacterial profile different from that of individuals without untreated caries. Stimulated saliva samples from 621 participants of the Danish Health Examination Survey were analyzed using the Human Oral Microbe Identification Microarray technology. Samples from 174 individuals with dental caries and 447 from a control cohort were compared using frequency and levels of identified bacterial taxa/clusters as endpoints. Differences at taxon/cluster level were analyzed using Mann-Whitney's test with Benjamini-Hochberg correction for multiple comparisons. Principal component analysis was used to visualize bacterial community profiles. A reduced bacterial diversity was observed in samples from subjects with dental caries. Five bacterial taxa (Veillonella parvula, Veillonella atypica, Megasphaera micronuciformis, Fusobacterium periodontium and Achromobacter xylosoxidans) and one bacterial cluster (Leptotrichia sp. clones C3MKM102 and GT018-ot417/462) were less frequently found in the caries group (adjusted p value <0.01) while two bacterial taxa (Solobacterium moorei and Streptococcus salivarius) and three bacterial clusters (Streptococcus parasanguinis I and II and sp. clone BE024-ot057/411/721, Streptococcus parasanguinis I and II and sinensis-ot411/721/767, Streptococcus salivarius and sp. clone FO042-ot067/755) were present at significantly higher levels (adjusted p value <0.01). The principal component analysis displayed a marked difference in the bacterial community profiles between groups. Presence of manifest caries was associated with a reduced diversity and an altered salivary bacterial community profile. Our data support recent theories that ecological stress-induced changes of commensal microbial communities are involved in the shift from oral health to tooth decay. © 2014 S. Karger AG, Basel.


Bugge A.,University of Southern Denmark | El-Naaman B.,University of Southern Denmark | McMurray R.G.,University of North Carolina at Chapel Hill | Froberg K.,University of Southern Denmark | And 5 more authors.
Hormone Research in Paediatrics | Year: 2012

Aims: To evaluate the associations between inflammatory markers and clustering of cardiovascular disease (CVD) risk factors, and to examine how inflammatory markers and CVD risk are related to fatness and cardiorespiratory fitness (VO2peak) in adolescents. Methods: Body mass and height, skinfolds and blood pressure of 413 adolescents (mean age 13.4 ± 0.3 years) were measured. Circulating fasting levels of glucose, insulin, lipids, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)α, soluble TNF receptor-1 (sTNFR1), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1Ra) were measured. VO2peak was measured in progressive tests to exhaustion. CVD risk was expressed as a clustered z-score, summing standardized values of individual risk factors. Results: The clustered z-score was negatively associated with adiponectin and positively associated with CRP, IL-6 and TNFα (all p values <0.05). The associations with adiponectin, CRP and IL-6 were stronger for the fattest adolescents. VO2peak was negatively correlated with clustered z-score, adiponectin and IL-6 and positively related to systolic blood pressure. The sum of four skinfolds was inversely related to adiponectin and positively correlated to body mass index, systolic blood pressure, homeostasis model assessment, clustered z-score and CRP. Conclusion: In adolescents, CVD risk was associated with alternations in adiponectin, TNFα, CRP and IL-6, and related to both VO2peak and fatness. Copyright © 2012 S. Karger AG, Basel.


Mellgren K.,Queen Silvias Hospital for Children and Adolescents | Mellgren K.,Gothenburg University | Hedegaard C.J.,Institute for Inflammation Research | Schmiegelow K.,Copenhagen University | And 3 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2012

Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim of the present study was to screen for a broader spectrum of growth factors and inflammatory mediators and to compare the profiles in different subtypes of NHL in pediatric patients. Serum samples were collected at diagnosis from 31 pediatric patients diagnosed with NHL admitted at Rigshospitalet, Copenhagen, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis are associated with plasma levels of growth factors and inflammatory mediators at presentation. Copyright © 2012 by Lippincott Williams & Wilkins.

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