LAMBARÉNÉ, GABON--Results of a new study may shed light on why allergic disease is less frequent in Third World tropical countries where helminth infection is endemic. These results add a further layer of complexity to the hygiene hypothesis, which has been put forth to help explain the alarming rise in atopic disorders in developed countries.

HELMINTH INFESTATION MAY HEIGHTEN IL-10 PRODUCTION

Helminth infestation appears to heighten the production of anti-inflammatory cytokines, particularly interleukin (IL) 10, which plays an important role in controlling allergic outcome, the study found.[1] In the study, children infested with helminth parasites had high levels of IL-10 and a reduced risk of skin reactivity to house-dust mites.

"We have found that individuals with a high level of parasite-induced IL-10 are less likely to have a positive skin test to mites even when they have very high levels of IgE [immunoglobulin E] directed to house-dust mites," Maria Yazdanbakhsh, PhD, said in an interview with RESPIRATORY REVIEWS. "Chronic helminth infections are associated with high levels of IL-10. The IL-10 can work either by inhibiting pro-inflammatory T cells that react with allergens or by reducing the response of nonhematopoietic cells to inflammatory mediators," she said.

Dr. Yazdanbakhsh and colleagues examined the impact of chronic helminth infections on the prevalence of atopy in 520 Gabonese children, ages 5 to 14 years. Subjects received skin-prick tests to determine their reaction to house-dust mites and other allergens. The researchers also collected blood and urine samples to screen for parasite infections. More comprehensive immunological studies were performed in a subsample of 132 children who exhibited reactivity to house-dust mites.

IL-10 SUPPRESSES ATOPY

Children with evidence of helminth infection had a lower prevalence of positive skin reactions to house-dust mites than did children without the infection. In addition, infected children had significantly higher schistosome-antigen—specific concentrations of IL-10, and these high concentrations correlated negatively with skin reactions to house-dust mites. "There is a clear suggestion that the effect of IgE on skin-test reactivity is suppressed by the parasite-induced interleukin 10," the authors reported.

According to Dr. Yazdanbakhsh and her colleagues, these findings contradict the hygiene hypothesis, which holds that exposure to infections facilitates T-helper-1 (TH1) responses while reducing the expression of T-helper-2 (TH2) cytokines.

"The notion of using TH1 responses to counterbalance harmful TH2 responses basically needs to be reconsidered," suggested Dr. Yazdanbakhsh, of the Department of Parasitology at Leiden University Medical Centre, in the Netherlands.

Patrick G. Holt, DSc, suggests that this interpretation may actually be overly simplistic. In an accompanying editorial, he points out that viral and bacterial infections are believed to affect allergic sensitization by influencing the balance between TH1 and TH2 polarized immunological memory against allergens.[2] Yet in the Gabon study, "the key effects of helminths appear targeted at cellular mechanisms central to the effector phase of atopy, which are operative beyond the stage in the disease process involving TH1/TH2 regulation," said Dr. Holt, Deputy Director of the TVW Telethon Institute for Child Health Research, in West Perth, Western Australia. He suggests that the finding that parasite-induced IL-10 may protect against clinical expression of allergy in sensitized subjects provides a strong argument for further research aimed at harnessing the anti-inflammatory effects of IL-10 for therapeutic purposes.

--Deborah L. O'Connor

References
1. van den Biggelaar AHJ, van Ree R, Rodrigues LC, et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet. 2000;356:1723-1727.

2. Holt PG. Parasites, atopy, and the hygiene hypothesis: resolution of a paradox? Lancet. 2000;356:1699-1701.