Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine-producing cells and early atopy.

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. CONCLUSION: 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.

IgE and tumor necrosis factor in malaria infection.

IgE, the immunoglobulin instrumental in atopic diseases is also elevated in many infections. This paper reports on the occurrence and possible pathogenic role of IgE in human Plasmodium falciparum malaria, one of the most widely spread and severe infectious diseases world wide. Plasmodial infections induce IgE elevation in the blood of the majority of people living in malaria endemic areas and up to 5% of this IgE constitutes anti-malaria antibodies. Production of IgE is controlled by T cells and elevated IgE concentrations in the blood of malaria patients are the result of an increased ratio of T-helper 2 (Th2) over T-helper 1 (Th1) cells. The underlying Th1 to Th2 switch is controlled by a variety of environmental and genetic factors. The importance of the latter is demonstrated by the IgE levels occurring in monozygotic or dizygotic twins originating from malarious areas of Africa. While these levels were indistinguishable within monozygotic twin pairs, they were different within the dizygotic pairs. Comparison of the levels of total IgE or IgE anti-malaria antibodies in patients with uncomplicated malaria with those in patients with the severe form of the disease (cerebral malaria or severe malaria without cerebral involvement) indicate that these levels are significantly higher in the cases with severe disease. This is the reverse with IgG and suggests that IgE plays a role in malaria pathogenesis. An important pathogenic mediator causing malaria fever and tissue lesions is tumor necrosis factor (TNF), generally believed to be induced by toxins released from the parasite. However, sera from malaria patients can also cause TNF release from monocytes in a reaction dependent on the presence of IgE containing immune complexes or aggregates. This results in induction and cross-linking of Fcepsilon receptor II (CD23) and by binding to and activating these cells, IgE will contribute to a local over-production of TNF in capillaries and post-capillary venules where P. falciparum parasites or their products accumulate in the severe forms of this disease.