Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations

Introduction The triggering of severe dengue has been associated with an exacerbated inflammatory process characterized by the production of pro-inflammatory cytokines such as IL-1β/IL-18, which are the product of inflammasome activation. Furthermore, alteration in the levels of high-density (HDL) a...

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Autores:
Marín Palma, Damariz
Sirois, Cherilyn Manuela
Urcuqui Inchima, Silvio
Hernández López, Juan Carlos
Tipo de recurso:
Article of journal
Fecha de publicación:
2019
Institución:
Universidad Cooperativa de Colombia
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Repositorio UCC
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OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/16021
Acceso en línea:
https://hdl.handle.net/20.500.12494/16021
Palabra clave:
Dengue
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repository_id_str
dc.title.spa.fl_str_mv Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
title Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
spellingShingle Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
Dengue
title_short Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
title_full Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
title_fullStr Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
title_full_unstemmed Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
title_sort Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations
dc.creator.fl_str_mv Marín Palma, Damariz
Sirois, Cherilyn Manuela
Urcuqui Inchima, Silvio
Hernández López, Juan Carlos
dc.contributor.author.none.fl_str_mv Marín Palma, Damariz
Sirois, Cherilyn Manuela
Urcuqui Inchima, Silvio
Hernández López, Juan Carlos
dc.subject.spa.fl_str_mv Dengue
topic Dengue
description Introduction The triggering of severe dengue has been associated with an exacerbated inflammatory process characterized by the production of pro-inflammatory cytokines such as IL-1β/IL-18, which are the product of inflammasome activation. Furthermore, alteration in the levels of high-density (HDL) and low-density lipoproteins (LDL) has been observed; and HDL are known to have immunomodulatory properties, including the regulation of inflammasomes. While HDL would be expected to counteract hyperactivation of the inflammasome, the relationship between HDL and dengue severity, has not previously been explored. Methodology We conducted a cross-sectional study of 30 patients with dengue and 39 healthy controls matched by sex and age. Lipid profile and levels of C-reactive protein were quantified. Serum levels of IL-1β, IL-6, IL-10, IL-18, and TNF-α, were assessed by ELISA. Expression of inflammasome-related genes in PBMC was quantified by qPCR. Results Dengue patients presented an alteration in the parameters of the lipid profile, with a significant decrease in HDL levels, which was more pronounced in dengue patients with warning signs. Moreover, a decrease in the expression of the inflammasome-related genes NLRP1, NLRC4, caspase-1, IL-1β and IL-18 was observed, as well as an increase in serum levels of C-reactive protein and IL-10 in dengue patients versus healthy donors. Significant positive correlations between LDL levels and the relative expression of NLRP3, NLRC4, IL-1β and IL-18, were found. Conclusion The results suggest that there is a relationship between the alteration of LDL and HDL with the imbalance in the inflammatory response, which could be associated with the severity of dengue.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019-03-22
dc.date.accessioned.none.fl_str_mv 2020-01-16T22:32:05Z
dc.date.available.none.fl_str_mv 2020-01-16T22:32:05Z
dc.type.none.fl_str_mv Artículo
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dc.identifier.uri.spa.fl_str_mv 10.1371/ journal.pone.0214245
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/16021
dc.identifier.bibliographicCitation.spa.fl_str_mv Marin-Palma D., Sirois C.M., Urcuqui- Inchima S. y Hernandez J.C. (2019) Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations. PLoS ONE 14(3): e0214245. https://doi.org/10.1371/ journal.pone.0214245. Recuperado de:
identifier_str_mv 10.1371/ journal.pone.0214245
Marin-Palma D., Sirois C.M., Urcuqui- Inchima S. y Hernandez J.C. (2019) Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations. PLoS ONE 14(3): e0214245. https://doi.org/10.1371/ journal.pone.0214245. Recuperado de:
url https://hdl.handle.net/20.500.12494/16021
dc.relation.isversionof.spa.fl_str_mv https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214245
dc.relation.ispartofjournal.spa.fl_str_mv PLoS ONE
dc.relation.references.spa.fl_str_mv 1. (TDR) WHOWatSPfRaTiTD. Dengue guidelines for diagnosis, treatment, prevention and control. 2009.
2. Dejnirattisai W, Jumnainsong A, Onsirisakul N, Fitton P, Vasanawathana S, Limpitikul W, et al. Cross-reacting antibodies enhance dengue virus infection in humans. Science. 2010;328(5979):745–8. pmid:20448183
3. Ng JK, Zhang SL, Tan HC, Yan B, Martinez JM, Tan WY, et al. First experimental in vivo model of enhanced dengue disease severity through maternally acquired heterotypic dengue antibodies. PLoS pathogens. 2014;10(4):e1004031. pmid:24699622
4. Kuczera D, Assolini JP, Tomiotto-Pellissier F, Pavanelli WR, Silveira GF. Highlights for Dengue Immunopathogenesis: Antibody-Dependent Enhancement, Cytokine Storm, and Beyond. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2018;38(2):69–80. pmid:29443656
5. Bethell DB, Flobbe K, Cao XT, Day NP, Pham TP, Buurman WA, et al. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. The Journal of infectious diseases. 1998;177(3):778–82 pmid:9498463
6. Lee WL, Liles WC. Endothelial activation, dysfunction and permeability during severe infections. Current opinion in hematology. 2011;18(3):191–6. pmid:21423012
7. Nascimento EJ, Braga-Neto U, Calzavara-Silva CE, Gomes AL, Abath FG, Brito CA, et al. Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome. PLoS One. 2009;4(11):e7892. pmid:19936257
8. Nascimento EJ, Silva AM, Cordeiro MT, Brito CA, Gil LH, Braga-Neto U, et al. Alternative complement pathway deregulation is correlated with dengue severity. PLoS One. 2009;4(8):e6782. pmid:19707565
9. Biswas HH, Gordon A, Nunez A, Perez MA, Balmaseda A, Harris E. Lower Low-Density Lipoprotein Cholesterol Levels Are Associated with Severe Dengue Outcome. PLoS neglected tropical diseases. 2015;9(9):e0003904. pmid:26334914
10. Duran A, Carrero R, Parra B, Gonzalez A, Delgado L, Mosquera J, et al. Association of lipid profile alterations with severe forms of dengue in humans. Archives of virology. 2015;160(7):1687–92. pmid:25936955
11. van Gorp EC, Suharti C, Mairuhu AT, Dolmans WM, van Der Ven J, Demacker PN, et al. Changes in the plasma lipid profile as a potential predictor of clinical outcome in dengue hemorrhagic fever. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2002;34(8):1150–3. pmid:11915007
12. Asztalos BF, de la Llera-Moya M, Dallal GE, Horvath KV, Schaefer EJ, Rothblat GH. Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux. J Lipid Res. 2005;46(10):2246–53. pmid:16061948
13. Marín-Palma D TN, Urcuqui-Inchima S, Hernández JC. Inflamación y respuesta inmune innata: Participación de las lipoproteínas de alta densidad. IATREIA. 2017 Oct-Dic;30(4):423–35.
14. Uittenbogaard A, Shaul PW, Yuhanna IS, Blair A, Smart EJ. High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J Biol Chem. 2000;275(15):11278–83 pmid:10753938
15. Kameda T, Ohkawa R, Yano K, Usami Y, Miyazaki A, Matsuda K, et al. Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein. Journal of lipids. 2015;2015:592594. pmid:26257958
16. Nofer JR, Levkau B, Wolinska I, Junker R, Fobker M, von Eckardstein A, et al. Suppression of endothelial cell apoptosis by high density lipoproteins (HDL) and HDL-associated lysosphingolipids. J Biol Chem. 2001;276(37):34480–5. pmid:11432865
17. Thacker SG, Zarzour A, Chen Y, Alcicek MS, Freeman LA, Sviridov DO, et al. High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation. Immunology. 2016;149(3):306–19. pmid:27329564
18. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nature reviews Immunology. 2016;16(7):407–20. pmid:27291964
19. Im H, Ammit AJ. The NLRP3 inflammasome: role in airway inflammation. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2014;44(2):160–72. pmid:24118105
20. Feria MG, Taborda NA, Hernandez JC, Rugeles MT. HIV replication is associated to inflammasomes activation, IL-1beta, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS One. 2018;13(4):e0192845. pmid:29672590
21. Bozza FA, Cruz OG, Zagne SM, Azeredo EL, Nogueira RM, Assis EF, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC infectious diseases. 2008;8:86. pmid:18578883
22. Mustafa AS, Elbishbishi EA, Agarwal R, Chaturvedi UC. Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever. FEMS immunology and medical microbiology. 2001;30(3):229–33 pmid:11335143
23. Wu MF, Chen ST, Yang AH, Lin WW, Lin YL, Chen NJ, et al. CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages. Blood. 2013;121(1):95–106. pmid:23152543
24. Hottz ED, Lopes JF, Freitas C, Valls-de-Souza R, Oliveira MF, Bozza MT, et al. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation. Blood. 2013;122(20):3405–14. pmid:24009231
25. Barrientos-Arenas E, Henao-García V, Giraldo DM, Cardona MM, Urcuqui-Inchima S, Castaño JC, et al. Modulación de los niveles de lipoproteínas de alta densidad y las citoquinas IL-1β e IL-6 en pacientes con dengue. Revista peruana de medicina experimental y salud publica. 2018;35 (1):15–24. pmid:29924262
26. Diseases WHOSPfRaTiT. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. 2009. Available from: http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf
27. Marin-Palma D, Castro GA, Cardona-Arias JA, Urcuqui-Inchima S, Hernandez JC. Lower High-Density Lipoproteins Levels During Human Immunodeficiency Virus Type 1 Infection Are Associated With Increased Inflammatory Markers and Disease Progression. Frontiers in immunology. 2018;9:1350. pmid:29963050
28. Gomez DM, Urcuqui-Inchima S, Hernandez JC. Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells. Innate Immun. 2017;23(8):697–708. pmid:29113588
29. Hernandez JC, Giraldo DM, Paul S, Urcuqui-Inchima S. Involvement of neutrophil hyporesponse and the role of Toll-like receptors in human immunodeficiency virus 1 protection. PLoS One. 2015;10(3):e0119844. pmid:25785697
30. Estruch M, Rajamaki K, Sanchez-Quesada JL, Kovanen PT, Oorni K, Benitez S, et al. Electronegative LDL induces priming and inflammasome activation leading to IL-1beta release in human monocytes and macrophages. Biochimica et biophysica acta. 2015;1851(11):1442–9. pmid:26327597
31. Garcia Cordero J, Leon Juarez M, Gonzalez YMJA, Cedillo Barron L, Gutierrez Castaneda B. Caveolin-1 in lipid rafts interacts with dengue virus NS3 during polyprotein processing and replication in HMEC-1 cells. PLoS One. 2014;9(3):e90704. pmid:24643062
32. Martinez-Gutierrez M, Castellanos JE, Gallego-Gomez JC. Statins reduce dengue virus production via decreased virion assembly. Intervirology. 2011;54(4):202–16. pmid:21293097
33. Carro AC, Damonte EB. Requirement of cholesterol in the viral envelope for dengue virus infection. Virus research. 2013;174(1–2):78–87. pmid:23517753
34. Murphy AJ, Woollard KJ, Hoang A, Mukhamedova N, Stirzaker RA, McCormick SP, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol. 2008;28(11):2071–7. pmid:18617650
35. Cui L, Lee YH, Kumar Y, Xu F, Lu K, Ooi EE, et al. Serum metabolome and lipidome changes in adult patients with primary dengue infection. PLoS neglected tropical diseases. 2013;7(8):e2373. pmid:23967362
36. Ekchariyawat P, Hamel R, Bernard E, Wichit S, Surasombatpattana P, Talignani L, et al. Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2015;32:401–8. pmid:25847693
37. Chaturvedi UC, Elbishbishi EA, Agarwal R, Raghupathy R, Nagar R, Tandon R, et al. Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures. Journal of medical virology. 1999;59(3):335–40 pmid:10502266
38. Azeredo EL, Zagne SM, Santiago MA, Gouvea AS, Santana AA, Neves-Souza PC, et al. Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. Immunobiology. 2001;204(4):494–507. pmid:11776403
39. Tauseef A, Umar N, Sabir S, Akmal A, Sajjad S, Zulfiqar S. Interleukin-10 as a Marker of Disease Progression in Dengue Hemorrhagic Fever. Journal of the College of Physicians and Surgeons—Pakistan: JCPSP. 2016;26(3):187–90. pmid:26975948
40. Suharti C, van Gorp EC, Dolmans WM, Setiati TE, Hack CE, Djokomoeljanto R, et al. Cytokine patterns during dengue shock syndrome. European cytokine network. 2003;14(3):172–7 pmid:14656693
41. Kuno G, Bailey RE. Cytokine responses to dengue infection among Puerto Rican patients. Memorias do Instituto Oswaldo Cruz. 1994;89(2):179–82 pmid:7885241
42. Chen JP, Lu HL, Lai SL, Campanella GS, Sung JM, Lu MY, et al. Dengue virus induces expression of CXC chemokine ligand 10/IFN-gamma-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate. J Immunol. 2006;177(5):3185–92 pmid:16920957
43. Brasier AR, Ju H, Garcia J, Spratt HM, Victor SS, Forshey BM, et al. A three-component biomarker panel for prediction of dengue hemorrhagic fever. The American journal of tropical medicine and hygiene. 2012;86(2):341–8. pmid:22302872
44. Eppy Suhendro, Nainggolan L, Rumende CM. The Differences Between Interleukin-6 and C-reactive Protein Levels Among Adult Patients of Dengue Infection with and without Plasma Leakage. Acta medica Indonesiana. 2016;48(1):3–9 pmid:27241538
45. Liu W, Yin Y, Zhou Z, He M, Dai Y. OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation. Inflammation research: official journal of the European Histamine Research Society [et al]. 2014;63(1):33–43. pmid:24121974
46. Soto-Acosta R, Mosso C, Cervantes-Salazar M, Puerta-Guardo H, Medina F, Favari L, et al. The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity. Virology. 2013;442(2):132–47. pmid:23642566
47. Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP, Phillips MC, et al. Crystallization of free cholesterol in model macrophage foam cells. Arterioscler Thromb Vasc Biol. 1999;19(8):1891–8 pmid:10446067
48. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61. pmid:20428172
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spelling Marín Palma, DamarizSirois, Cherilyn ManuelaUrcuqui Inchima, SilvioHernández López, Juan Carlos14(3)2020-01-16T22:32:05Z2020-01-16T22:32:05Z2019-03-2210.1371/ journal.pone.0214245https://hdl.handle.net/20.500.12494/16021Marin-Palma D., Sirois C.M., Urcuqui- Inchima S. y Hernandez J.C. (2019) Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations. PLoS ONE 14(3): e0214245. https://doi.org/10.1371/ journal.pone.0214245. Recuperado de:Introduction The triggering of severe dengue has been associated with an exacerbated inflammatory process characterized by the production of pro-inflammatory cytokines such as IL-1β/IL-18, which are the product of inflammasome activation. Furthermore, alteration in the levels of high-density (HDL) and low-density lipoproteins (LDL) has been observed; and HDL are known to have immunomodulatory properties, including the regulation of inflammasomes. While HDL would be expected to counteract hyperactivation of the inflammasome, the relationship between HDL and dengue severity, has not previously been explored. Methodology We conducted a cross-sectional study of 30 patients with dengue and 39 healthy controls matched by sex and age. Lipid profile and levels of C-reactive protein were quantified. Serum levels of IL-1β, IL-6, IL-10, IL-18, and TNF-α, were assessed by ELISA. Expression of inflammasome-related genes in PBMC was quantified by qPCR. Results Dengue patients presented an alteration in the parameters of the lipid profile, with a significant decrease in HDL levels, which was more pronounced in dengue patients with warning signs. Moreover, a decrease in the expression of the inflammasome-related genes NLRP1, NLRC4, caspase-1, IL-1β and IL-18 was observed, as well as an increase in serum levels of C-reactive protein and IL-10 in dengue patients versus healthy donors. Significant positive correlations between LDL levels and the relative expression of NLRP3, NLRC4, IL-1β and IL-18, were found. Conclusion The results suggest that there is a relationship between the alteration of LDL and HDL with the imbalance in the inflammatory response, which could be associated with the severity of dengue.https://scienti.colciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000283088http://orcid.org/0000-0002-9200-5698https://scienti.colciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000011355juanc.hernandezl@campusucc.edu.coe0214245Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina, Medellín y EnvigadoMedicinaMedellínhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214245PLoS ONE1. (TDR) WHOWatSPfRaTiTD. Dengue guidelines for diagnosis, treatment, prevention and control. 2009.2. Dejnirattisai W, Jumnainsong A, Onsirisakul N, Fitton P, Vasanawathana S, Limpitikul W, et al. Cross-reacting antibodies enhance dengue virus infection in humans. Science. 2010;328(5979):745–8. pmid:204481833. Ng JK, Zhang SL, Tan HC, Yan B, Martinez JM, Tan WY, et al. First experimental in vivo model of enhanced dengue disease severity through maternally acquired heterotypic dengue antibodies. PLoS pathogens. 2014;10(4):e1004031. pmid:246996224. Kuczera D, Assolini JP, Tomiotto-Pellissier F, Pavanelli WR, Silveira GF. Highlights for Dengue Immunopathogenesis: Antibody-Dependent Enhancement, Cytokine Storm, and Beyond. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2018;38(2):69–80. pmid:294436565. Bethell DB, Flobbe K, Cao XT, Day NP, Pham TP, Buurman WA, et al. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. The Journal of infectious diseases. 1998;177(3):778–82 pmid:94984636. Lee WL, Liles WC. Endothelial activation, dysfunction and permeability during severe infections. Current opinion in hematology. 2011;18(3):191–6. pmid:214230127. Nascimento EJ, Braga-Neto U, Calzavara-Silva CE, Gomes AL, Abath FG, Brito CA, et al. Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome. PLoS One. 2009;4(11):e7892. pmid:199362578. Nascimento EJ, Silva AM, Cordeiro MT, Brito CA, Gil LH, Braga-Neto U, et al. Alternative complement pathway deregulation is correlated with dengue severity. PLoS One. 2009;4(8):e6782. pmid:197075659. Biswas HH, Gordon A, Nunez A, Perez MA, Balmaseda A, Harris E. Lower Low-Density Lipoprotein Cholesterol Levels Are Associated with Severe Dengue Outcome. PLoS neglected tropical diseases. 2015;9(9):e0003904. pmid:2633491410. Duran A, Carrero R, Parra B, Gonzalez A, Delgado L, Mosquera J, et al. Association of lipid profile alterations with severe forms of dengue in humans. Archives of virology. 2015;160(7):1687–92. pmid:2593695511. van Gorp EC, Suharti C, Mairuhu AT, Dolmans WM, van Der Ven J, Demacker PN, et al. Changes in the plasma lipid profile as a potential predictor of clinical outcome in dengue hemorrhagic fever. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2002;34(8):1150–3. pmid:1191500712. Asztalos BF, de la Llera-Moya M, Dallal GE, Horvath KV, Schaefer EJ, Rothblat GH. Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux. J Lipid Res. 2005;46(10):2246–53. pmid:1606194813. Marín-Palma D TN, Urcuqui-Inchima S, Hernández JC. Inflamación y respuesta inmune innata: Participación de las lipoproteínas de alta densidad. IATREIA. 2017 Oct-Dic;30(4):423–35.14. Uittenbogaard A, Shaul PW, Yuhanna IS, Blair A, Smart EJ. High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J Biol Chem. 2000;275(15):11278–83 pmid:1075393815. Kameda T, Ohkawa R, Yano K, Usami Y, Miyazaki A, Matsuda K, et al. Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein. Journal of lipids. 2015;2015:592594. pmid:2625795816. Nofer JR, Levkau B, Wolinska I, Junker R, Fobker M, von Eckardstein A, et al. Suppression of endothelial cell apoptosis by high density lipoproteins (HDL) and HDL-associated lysosphingolipids. J Biol Chem. 2001;276(37):34480–5. pmid:1143286517. Thacker SG, Zarzour A, Chen Y, Alcicek MS, Freeman LA, Sviridov DO, et al. High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation. Immunology. 2016;149(3):306–19. pmid:2732956418. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nature reviews Immunology. 2016;16(7):407–20. pmid:2729196419. Im H, Ammit AJ. The NLRP3 inflammasome: role in airway inflammation. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2014;44(2):160–72. pmid:2411810520. Feria MG, Taborda NA, Hernandez JC, Rugeles MT. HIV replication is associated to inflammasomes activation, IL-1beta, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS One. 2018;13(4):e0192845. pmid:2967259021. Bozza FA, Cruz OG, Zagne SM, Azeredo EL, Nogueira RM, Assis EF, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC infectious diseases. 2008;8:86. pmid:1857888322. Mustafa AS, Elbishbishi EA, Agarwal R, Chaturvedi UC. Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever. 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