title: Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria.
abstract: BACKGROUND
  During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy-associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity acquired prior to first pregnancy have not been studied in detail previously, and were the topic of the present study.
  
  
  METHODS
  A multiplexed bead assay was used to measure plasma levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF in BALB/c mice immunized against P. berghei K173 by repeated infection and drug cure before the first pregnancy. The association between cytokine levels on the one hand and parasitaemia and haemoglobin levels on the other, in mice that had never been pregnant or were pregnant for the first, second or third time were evaluated by Mann-Whitney test and Spearman rank-order correlation analysis.
  
  
  RESULTS
  Pregnancy per se did not further increase the already high cytokine levels in mice previously immunized by repeated infection and drug cure. Levels of all the cytokines except IL-10 were correlated with each other, and with parasitaemia and haemoglobin levels. Furthermore, levels of all cytokines were positively correlated with parity, except IL-10, which was negatively correlated with parity. High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome.
  
  
  CONCLUSIONS
  High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome in this mouse model of placental malaria. Since the model replicates key parasitological and immunological features of placental P. falciparum malaria, it underpins its usefulness in immunology and pathogenesis studies of this important cause of mother/child morbidity in endemic areas.
authors.forename: Rosette
authors.initials: R
authors.lastname: Megnekou
authors.forename: Trine
authors.initials: T
authors.lastname: Staalsoe
authors.affiliation: Centre for Medical Parasitology, Department of Clinical Microbiology and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet) and Institute for International Health, Immunology, and Microbiology, CSS Building 22, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark. lhviid@sund.ku.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Hviid
mesh_terms: D000328:Adult; D000818:Animals; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000276:immunology* / Q000469:parasitology; D010949:Plasma / Q000737:chemistry; D010962:Plasmodium berghei / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000469:parasitology; D012008:Recurrence
chemical_list: D016207:Cytokines