Skip to main content
Top
Published in: Malaria Journal 1/2008

Open Access 01-12-2008 | Research

Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria

Authors: Edward R Kabyemela, Atis Muehlenbachs, Michal Fried, Jonathan D Kurtis, Theonest K Mutabingwa, Patrick E Duffy

Published in: Malaria Journal | Issue 1/2008

Login to get access

Abstract

Background

Placental malaria (PM) is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation.

Methods

In a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined.

Results

Peripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-γ, IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers.

Conclusion

These data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E, Hirt R, Cardesa A, Alonso PL: Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Human pathology. 2000, 31 (1): 85-93. 10.1016/S0046-8177(00)80203-8.CrossRefPubMed Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E, Hirt R, Cardesa A, Alonso PL: Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Human pathology. 2000, 31 (1): 85-93. 10.1016/S0046-8177(00)80203-8.CrossRefPubMed
2.
go back to reference Fried M, Duffy PE: Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996, 272 (): 1502-1504. 10.1126/science.272.5267.1502.CrossRefPubMed Fried M, Duffy PE: Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996, 272 (): 1502-1504. 10.1126/science.272.5267.1502.CrossRefPubMed
3.
go back to reference Bulmer JN, Rasheed FN, Francis N, Morrison L, Greenwood BM: Placental malaria. I. Pathological classification. Histopathology. 1993, 22 (3): 211-218. 10.1111/j.1365-2559.1993.tb00110.x.CrossRefPubMed Bulmer JN, Rasheed FN, Francis N, Morrison L, Greenwood BM: Placental malaria. I. Pathological classification. Histopathology. 1993, 22 (3): 211-218. 10.1111/j.1365-2559.1993.tb00110.x.CrossRefPubMed
4.
go back to reference Duffy PE: Immunity to malaria during pregnancy: different host, different parasite: London, New York.Edited by: Duffy PEFM. 2001, Taylor & Francis, 71-126. 1st, Duffy PE: Immunity to malaria during pregnancy: different host, different parasite: London, New York.Edited by: Duffy PEFM. 2001, Taylor & Francis, 71-126. 1st,
5.
go back to reference Fried M, Muga RO, Misore AO, Duffy PE: Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. J Immunol. 1998, 160 (5): 2523-2530.PubMed Fried M, Muga RO, Misore AO, Duffy PE: Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. J Immunol. 1998, 160 (5): 2523-2530.PubMed
6.
go back to reference Mockenhaupt FP, Ulmen U, von Gaertner C, Bedu-Addo G, Bienzle U: Diagnosis of placental malaria. Journal of clinical microbiology. 2002, 40 (1): 306-308. 10.1128/JCM.40.1.306-308.2002.PubMedCentralCrossRefPubMed Mockenhaupt FP, Ulmen U, von Gaertner C, Bedu-Addo G, Bienzle U: Diagnosis of placental malaria. Journal of clinical microbiology. 2002, 40 (1): 306-308. 10.1128/JCM.40.1.306-308.2002.PubMedCentralCrossRefPubMed
7.
go back to reference Mockenhaupt FP, Bedu-Addo G, von Gaertner C, Boye R, Fricke K, Hannibal I, Karakaya F, Schaller M, Ulmen U, Acquah PA, Dietz E, Eggelte TA, Bienzle U: Detection and clinical manifestation of placental malaria in southern Ghana. Malaria journal. 2006, 5: 119-10.1186/1475-2875-5-119.PubMedCentralCrossRefPubMed Mockenhaupt FP, Bedu-Addo G, von Gaertner C, Boye R, Fricke K, Hannibal I, Karakaya F, Schaller M, Ulmen U, Acquah PA, Dietz E, Eggelte TA, Bienzle U: Detection and clinical manifestation of placental malaria in southern Ghana. Malaria journal. 2006, 5: 119-10.1186/1475-2875-5-119.PubMedCentralCrossRefPubMed
8.
go back to reference Ostrowski SR, Shulman CE, Peshu N, Staalsoe T, Hoyer-Hansen G, Pedersen BK, Marsh K, Ullum H: Elevated plasma urokinase receptor predicts low birth weight in maternal malaria. Parasite immunology. 2007, 29 (1): 37-46. 10.1111/j.1365-3024.2006.00916.x.CrossRefPubMed Ostrowski SR, Shulman CE, Peshu N, Staalsoe T, Hoyer-Hansen G, Pedersen BK, Marsh K, Ullum H: Elevated plasma urokinase receptor predicts low birth weight in maternal malaria. Parasite immunology. 2007, 29 (1): 37-46. 10.1111/j.1365-3024.2006.00916.x.CrossRefPubMed
9.
go back to reference Coutinho HM, McGarvey ST, Acosta LP, Manalo DL, Langdon GC, Leenstra T, Kanzaria HK, Solomon J, Wu H, Olveda RM, Kurtis JD, Friedman JF: Nutritional status and serum cytokine profiles in children, adolescents, and young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte, Philippines. The Journal of infectious diseases. 2005, 192 (3): 528-536. 10.1086/430929.CrossRef Coutinho HM, McGarvey ST, Acosta LP, Manalo DL, Langdon GC, Leenstra T, Kanzaria HK, Solomon J, Wu H, Olveda RM, Kurtis JD, Friedman JF: Nutritional status and serum cytokine profiles in children, adolescents, and young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte, Philippines. The Journal of infectious diseases. 2005, 192 (3): 528-536. 10.1086/430929.CrossRef
10.
go back to reference Muehlenbachs A, Fried M, Lachowitzer J, Mutabingwa TK, Duffy PE: Genome-wide expression analysis of placental malaria reveals features of lymphoid neogenesis during chronic infection. J Immunol. 2007, 179 (1): 557-565.CrossRefPubMed Muehlenbachs A, Fried M, Lachowitzer J, Mutabingwa TK, Duffy PE: Genome-wide expression analysis of placental malaria reveals features of lymphoid neogenesis during chronic infection. J Immunol. 2007, 179 (1): 557-565.CrossRefPubMed
12.
go back to reference de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. The Journal of experimental medicine. 1991, 174 (5): 1209-1220. 10.1084/jem.174.5.1209.CrossRefPubMed de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. The Journal of experimental medicine. 1991, 174 (5): 1209-1220. 10.1084/jem.174.5.1209.CrossRefPubMed
13.
go back to reference Gazzinelli RT, Oswald IP, James SL, Sher A: IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. J Immunol. 1992, 148 (6): 1792-1796.PubMed Gazzinelli RT, Oswald IP, James SL, Sher A: IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. J Immunol. 1992, 148 (6): 1792-1796.PubMed
14.
go back to reference Silva JS, Morrissey PJ, Grabstein KH, Mohler KM, Anderson D, Reed SG: Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. The Journal of experimental medicine. 1992, 175 (1): 169-174. 10.1084/jem.175.1.169.CrossRefPubMed Silva JS, Morrissey PJ, Grabstein KH, Mohler KM, Anderson D, Reed SG: Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. The Journal of experimental medicine. 1992, 175 (1): 169-174. 10.1084/jem.175.1.169.CrossRefPubMed
15.
go back to reference Heinzel FP, Sadick MD, Mutha SS, Locksley RM: Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proceedings of the National Academy of Sciences of the United States of America. 1991, 88 (16): 7011-7015. 10.1073/pnas.88.16.7011.PubMedCentralCrossRefPubMed Heinzel FP, Sadick MD, Mutha SS, Locksley RM: Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proceedings of the National Academy of Sciences of the United States of America. 1991, 88 (16): 7011-7015. 10.1073/pnas.88.16.7011.PubMedCentralCrossRefPubMed
16.
go back to reference Sher A, Fiorentino D, Caspar P, Pearce E, Mosmann T: Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991, 147 (8): 2713-2716.PubMed Sher A, Fiorentino D, Caspar P, Pearce E, Mosmann T: Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991, 147 (8): 2713-2716.PubMed
17.
go back to reference Bogdan C, Vodovotz Y, Nathan C: Macrophage deactivation by interleukin 10. The Journal of experimental medicine. 1991, 174 (6): 1549-1555. 10.1084/jem.174.6.1549.CrossRefPubMed Bogdan C, Vodovotz Y, Nathan C: Macrophage deactivation by interleukin 10. The Journal of experimental medicine. 1991, 174 (6): 1549-1555. 10.1084/jem.174.6.1549.CrossRefPubMed
18.
go back to reference Rockett KA, Awburn MM, Cowden WB, Clark IA: Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun. 1991, 59 (): 3280-3283.PubMedCentralPubMed Rockett KA, Awburn MM, Cowden WB, Clark IA: Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun. 1991, 59 (): 3280-3283.PubMedCentralPubMed
19.
go back to reference Wenisch C, Parschalk B, Narzt E, Looareesuwan S, Graninger W: Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria. Clinical immunology and immunopathology. 1995, 74 (1): 115-117. 10.1006/clin.1995.1017.CrossRefPubMed Wenisch C, Parschalk B, Narzt E, Looareesuwan S, Graninger W: Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria. Clinical immunology and immunopathology. 1995, 74 (1): 115-117. 10.1006/clin.1995.1017.CrossRefPubMed
20.
go back to reference Gosi P, Khusmith S, Looareesuwan S, Sitachamroom U, Glanarongran R, Buchachart K, Walsh DS: Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15. The Southeast Asian journal of tropical medicine and public health. 1999, 30 (3): 412-417.PubMed Gosi P, Khusmith S, Looareesuwan S, Sitachamroom U, Glanarongran R, Buchachart K, Walsh DS: Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15. The Southeast Asian journal of tropical medicine and public health. 1999, 30 (3): 412-417.PubMed
21.
go back to reference Suguitan AL, Leke RG, Fouda G, Zhou A, Thuita L, Metenou S, Fogako J, Megnekou R, Taylor DW: Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. The Journal of infectious diseases. 2003, 188 (7): 1074-1082. 10.1086/378500.CrossRefPubMed Suguitan AL, Leke RG, Fouda G, Zhou A, Thuita L, Metenou S, Fogako J, Megnekou R, Taylor DW: Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. The Journal of infectious diseases. 2003, 188 (7): 1074-1082. 10.1086/378500.CrossRefPubMed
22.
go back to reference Kurtzhals JA, Adabayeri V, Goka BQ, Akanmori BD, Oliver-Commey JO, Nkrumah FK, Behr C, Hviid L: Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria. Lancet. 1998, 351 (9118): 1768-1772. 10.1016/S0140-6736(97)09439-7.CrossRefPubMed Kurtzhals JA, Adabayeri V, Goka BQ, Akanmori BD, Oliver-Commey JO, Nkrumah FK, Behr C, Hviid L: Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria. Lancet. 1998, 351 (9118): 1768-1772. 10.1016/S0140-6736(97)09439-7.CrossRefPubMed
23.
go back to reference Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhayakumar V: A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. The Journal of infectious diseases. 1999, 179 (1): 279-282. 10.1086/314548.CrossRefPubMed Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhayakumar V: A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. The Journal of infectious diseases. 1999, 179 (1): 279-282. 10.1086/314548.CrossRefPubMed
24.
go back to reference Hugosson E, Montgomery SM, Premji Z, Troye-Blomberg M, Bjorkman A: Higher IL-10 levels are associated with less effective clearance of Plasmodium falciparum parasites. Parasite immunology. 2004, 26 (3): 111-117. 10.1111/j.0141-9838.2004.00678.x.CrossRefPubMed Hugosson E, Montgomery SM, Premji Z, Troye-Blomberg M, Bjorkman A: Higher IL-10 levels are associated with less effective clearance of Plasmodium falciparum parasites. Parasite immunology. 2004, 26 (3): 111-117. 10.1111/j.0141-9838.2004.00678.x.CrossRefPubMed
25.
go back to reference Fried M, Domingo GJ, Gowda CD, Mutabingwa TK, Duffy PE: Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion of parasitized erythrocytes in the placenta. Experimental parasitology. 2006, 113 (1): 36-42. 10.1016/j.exppara.2005.12.003.CrossRefPubMed Fried M, Domingo GJ, Gowda CD, Mutabingwa TK, Duffy PE: Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion of parasitized erythrocytes in the placenta. Experimental parasitology. 2006, 113 (1): 36-42. 10.1016/j.exppara.2005.12.003.CrossRefPubMed
26.
go back to reference Urban BC, Cordery D, Shafi MJ, Bull PC, Newbold CI, Williams TN, Marsh K: The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infection and immunity. 2006, 74 (12): 6700-6706. 10.1128/IAI.00861-06.PubMedCentralCrossRefPubMed Urban BC, Cordery D, Shafi MJ, Bull PC, Newbold CI, Williams TN, Marsh K: The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infection and immunity. 2006, 74 (12): 6700-6706. 10.1128/IAI.00861-06.PubMedCentralCrossRefPubMed
27.
go back to reference Rogerson SJ, Brown HC, Pollina E, Abrams ET, Tadesse E, Lema VM, Molyneux ME: Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women. Infection and immunity. 2003, 71 (1): 267-270. 10.1128/IAI.71.1.267-270.2003.PubMedCentralCrossRefPubMed Rogerson SJ, Brown HC, Pollina E, Abrams ET, Tadesse E, Lema VM, Molyneux ME: Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women. Infection and immunity. 2003, 71 (1): 267-270. 10.1128/IAI.71.1.267-270.2003.PubMedCentralCrossRefPubMed
28.
go back to reference Das BS, Thurnham DI, Das DB: Influence of malaria on markers of iron status in children: implications for interpreting iron status in malaria-endemic communities. The British journal of nutrition. 1997, 78 (5): 751-760. 10.1079/BJN19970192.CrossRefPubMed Das BS, Thurnham DI, Das DB: Influence of malaria on markers of iron status in children: implications for interpreting iron status in malaria-endemic communities. The British journal of nutrition. 1997, 78 (5): 751-760. 10.1079/BJN19970192.CrossRefPubMed
29.
go back to reference Taylor PG, Martinez-Torres C, Mendez-Castellano H, Bosch V, Leets I, Tropper E, Layrisse M: The relationship between iron deficiency and anemia in Venezuelan children. The American journal of clinical nutrition. 1993, 58 (2): 215-218.PubMed Taylor PG, Martinez-Torres C, Mendez-Castellano H, Bosch V, Leets I, Tropper E, Layrisse M: The relationship between iron deficiency and anemia in Venezuelan children. The American journal of clinical nutrition. 1993, 58 (2): 215-218.PubMed
30.
go back to reference Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN: Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. The Journal of biological chemistry. 1990, 265 (24): 14572-14578.PubMed Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN: Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. The Journal of biological chemistry. 1990, 265 (24): 14572-14578.PubMed
Metadata
Title
Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria
Authors
Edward R Kabyemela
Atis Muehlenbachs
Michal Fried
Jonathan D Kurtis
Theonest K Mutabingwa
Patrick E Duffy
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2008
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-7-26

Other articles of this Issue 1/2008

Malaria Journal 1/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.