title: Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine-producing cells and early atopy.
abstract: BACKGROUND
  We have previously shown that Epstein-Barr virus (EBV) seropositivity, at 2 years of age, was inversely related to IgE-sensitization and that this effect was enhanced when EBV is combined with cytomegalovirus (CMV) seropositivity. We hypothesize that early exposure to EBV or CMV will affect the cytokine balance in the individual.
  
  
  OBJECTIVE
  The aim of this study was to relate the cytokine profile in peripheral blood mononuclear cells (PBMC) to the EBV and CMV serostatus and IgE-sensitization in children at 2 years of age.
  
  
  METHODS
  Seventy-five children were followed prospectively from birth until 2 years of age. Their EBV and CMV serostatus was correlated to the numbers of IFN-gamma, IL-4, IL-10 and IL-12-producing PBMC following PHA stimulation in vitro. Skin prick tests and allergen-specific IgE antibodies were used to assess IgE-sensitization.
  
  
  RESULTS
  In the study cohort, there was an inverse association between EBV seropositivity and IgE-sensitization but not with CMV seropositivity. Following linear regression analysis, we did not detect any statistically significant associations between children with IgG antibodies against EBV at 2 years of age and the investigated cytokines. However, there was a non-significant tendency to a positive association between high numbers of all individual cytokine-producing cells and EBV seropositivity. Children who were CMV seropositive had significantly higher numbers of IFN-gamma and lower numbers of IL-4-producing cells compared with CMV negative children. There was a significant, positive association between the number of IL-4-producing cells and IgE-sensitization.
  
  
  CONCLUSIONS
  Taken together our results indicate that infections with EBV and CMV in different ways will interact with the immune system and may protect children from developing early atopy.
authors.affiliation: Department of Clinical Science and Education, Karolinska Institutet, Sodersjukhuset, Stockholm, Sweden. caroline.nilsson@sodersjukhuset.se
authors.forename: C
authors.initials: C
authors.lastname: Nilsson
authors.forename: A-K
authors.initials: AK
authors.lastname: Larsson Sigfrinius
authors.forename: S M
authors.initials: SM
authors.lastname: Montgomery
authors.forename: E
authors.initials: E
authors.lastname: Sverremark-Ekström
authors.forename: A
authors.initials: A
authors.lastname: Linde
authors.forename: G
authors.initials: G
authors.lastname: Lilja
authors.forename: M T
authors.initials: MT
authors.lastname: Blomberg
mesh_terms: D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000821:virology*; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011446:Prospective Studies; D012882:Skin Tests
chemical_list: D016207:Cytokines; D010835:Phytohemagglutinins; D007073:Immunoglobulin E