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Publications (10 of 45) Show all publications
Thomas, A. M., Gerogianni, A., Barratt-Due, A., McAdam, M. B., Mollnes, T. E. & Nilsson, P. H. (2018). Complement (C5)-inhibition attenuates heme-induced inflammation in human whole blood. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM. Molecular Immunology, 102, 220-220
Open this publication in new window or tab >>Complement (C5)-inhibition attenuates heme-induced inflammation in human whole blood
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2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 220-220Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Complement, Heme, Inflammation, Thromboinflammation, Complement 5
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78411 (URN)10.1016/j.molimm.2018.06.228 (DOI)000445313600224 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-11-16Bibliographically approved
Orrem, H. L., Nilsson, P. H., Pischke, S. E., Kleveland, O., Yndestad, A., Ekholt, K., . . . Mollnes, T. E. (2018). IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction. Frontiers in Immunology, 9, Article ID 2035.
Open this publication in new window or tab >>IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2035Article in journal (Refereed) Published
Abstract [en]

Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p < 0.001) and substantially (> 50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
complement, C5a receptors, C3a receptor, IL-6, myocardial infarction, inflammation
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78097 (URN)10.3389/fimmu.2018.02035 (DOI)000444419300001 ()
Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-11-16Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P. H., Nilsson, B. & Nilsson Ekdahl, K. (2018). Is the polarized secretion of complement factor H of importance in age-related macular degeneration?. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
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2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
National Category
Ophthalmology
Research subject
Natural Science, Optometry
Identifiers
urn:nbn:se:lnu:diva-78425 (URN)000442932806149 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-11-16Bibliographically approved
Orrem, H. L., Shetelig, C., Ueland, T., Limalanathan, S., Nilsson, P. H., Husebye, T., . . . Yndestad, A. (2018). Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction. International Journal of Cardiology, 268, 187-192
Open this publication in new window or tab >>Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction
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2018 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 268, p. 187-192Article in journal (Refereed) Published
Abstract [en]

Background: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1 alpha and IL-1 beta are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n=65). Results: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI. (C 18 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Inflammation, Cytokine, Interleukin-1, Acute coronary syndromes, Myocardial infarction, Ventricular remodelling
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences; Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-77369 (URN)10.1016/j.ijcard.2018.05.032 (DOI)000439363400045 ()29853279 (PubMedID)
Available from: 2018-08-30 Created: 2018-08-30 Last updated: 2018-11-16Bibliographically approved
Wibroe, P. P., Anselmo, A. C., Nilsson, P. H., Sarode, A., Gupta, V., Urbanics, R., . . . Moghimi, S. M. (2017). Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes.. Nature Nanotechnology, 12(6), 589-594
Open this publication in new window or tab >>Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes.
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2017 (English)In: Nature Nanotechnology, ISSN 1748-3387, E-ISSN 1748-3395, Vol. 12, no 6, p. 589-594Article in journal (Refereed) Published
Abstract [en]

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-65207 (URN)10.1038/nnano.2017.47 (DOI)000402769100019 ()28396605 (PubMedID)
Available from: 2017-06-12 Created: 2017-06-12 Last updated: 2017-07-19Bibliographically approved
Nilsson, P. H., Johnson, C., Pischke, S. E., Fure, H., Landsem, A., Bergseth, G., . . . Mollnes, T. E. (2017). Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation. Paper presented at 16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017. Molecular Immunology, 89(SI: EMCHD2017), 136-137
Open this publication in new window or tab >>Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, no SI: EMCHD2017, p. 136-137Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-73372 (URN)10.1016/j.molimm.2017.06.075 (DOI)
Conference
16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-04-24Bibliographically approved
Nilsson, P. H., Johnson, C., Pischke, S. E., Fure, H., Landsem, A., Bergseth, G., . . . Mollnes, T. E. (2017). Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 136-137
Open this publication in new window or tab >>Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 136-137Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-68146 (URN)10.1016/j.molimm.2017.06.075 (DOI)000410014500056 ()
Conference
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-11-16Bibliographically approved
Thomas, A. M., Schjalm, C., Nilsson, P. H., Lindenskov, P. H., Rørtveit, R., Solberg, R., . . . Barratt-Due, A. (2017). Combined inhibition of C5 and CD14 attenuates systemic inflammation in a newborn pig-model of meconium aspiration syndrome. Paper presented at 16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017. Molecular Immunology, 89(SI: EMCHD2017), 166-167
Open this publication in new window or tab >>Combined inhibition of C5 and CD14 attenuates systemic inflammation in a newborn pig-model of meconium aspiration syndrome
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, no SI: EMCHD2017, p. 166-167Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-73374 (URN)10.1016/j.molimm.2017.06.140 (DOI)
Conference
16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-04-24Bibliographically approved
Mahmoudi, M., Nilsson, P. H., Mollnes, T. E., Roos, D. & Sullivan, K. E. (2017). Complement Deficiencies (2nded.). In: Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D (Ed.), Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management (pp. 437-460). Berlin, Heidelberg: Springer
Open this publication in new window or tab >>Complement Deficiencies
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2017 (English)In: Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management / [ed] Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D, Berlin, Heidelberg: Springer, 2017, 2nd, p. 437-460Chapter in book (Refereed)
Place, publisher, year, edition, pages
Berlin, Heidelberg: Springer, 2017 Edition: 2nd
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-60983 (URN)10.1007/978-3-662-52909-6_8 (DOI)9783662529096 (ISBN)9783662529072 (ISBN)
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2018-01-13Bibliographically approved
Barratt-Due, A., Pischke, S. E., Nilsson, P. H., Espevik, T. & Mollnes, T. E. (2017). Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets.. Journal of Leukocyte Biology, 101(1), 193-204
Open this publication in new window or tab >>Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets.
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2017 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 101, no 1, p. 193-204Article in journal (Refereed) Published
Abstract [en]

The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators involved in the pathogenesis of this condition. Instead, we have put forward a hypothesis of inhibition at the recognition phase by "dual blockade" of bottleneck molecules of complement and TLRs. By acting upstream and broadly, the dual blockade could be beneficial in conditions with improper or uncontrolled innate immune activation threatening the host. Key bottleneck molecules in these systems that could be targets for inhibition are the central complement molecules C3 and C5 and the important CD14 molecule, which is a coreceptor for several TLRs, including TLR4 and TLR2. This review summarizes current knowledge of inhibition of complement and TLRs alone and in combination, in both sterile and nonsterile inflammatory processes, where activation of these systems is of crucial importance for tissue damage and disease. Thus, dual blockade might provide a general, broad-acting therapeutic regimen against a number of diseases where innate immunity is improperly activated.

National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-60952 (URN)10.1189/jlb.3VMR0316-132R (DOI)000392148500018 ()27581539 (PubMedID)
Available from: 2017-02-26 Created: 2017-02-26 Last updated: 2018-05-31Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7192-5794

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