Gastrointestinal roundworm parasites within the genera Necator, Ancylostoma, Ascaris, Trichinella, and Strongyloides infect approximately 25% of humanity and cause considerable morbidity and mortality. Our investigations of mice infected with an enteric roundworm parasite, Heligmosomoides polygyrus, have revealed that specific cytokines are responsible for the development of eosinophilia, serum IgE responses, and mucosal mastocytosis: disease characteristics that these mice share with roundworm-infected humans. Most importantly, the cytokine IL-4 has been shown to be essential for immunity to a challenge infection. We have now used a quantitative reverse transcriptase-polymerase chain reaction (RT- PCR) technique to analyze in vivo cytokine gene expression in different lymphoid organs of H. polygyrus-infected mice. We have documented a vigorous cytokine response in Peyer's patch and mesenteric lymph node cells, but not in spleen cells. IL-3, IL-4, IL-5, and IL-9 gene expression are considerably elevated, while IL-2, IL-10, and IFN-gamma are not. We now plan to continue these studies by addressing the following issues: 1) Which cell types express, at both the mRNA and protein levels, the different cytokines? 2) How does cytokine expression differ in primary vs. challenge infections? 3) Do cytokines produced at early stages of infection influence the response at later stages of the primary and also in the challenge infection? 4) What cytokine responses are made early after infection by cells immediately proximate to parasite larvae? We believe that answers to these questions are obtainable with the RT-PCR and ELISPOT techniques that we have developed in our laboratories and with the in situ staining techniques that have been used by our collaborator, Eric Claassen. The answers obtained from these studies should be useful in the planning of therapeutic protocols to protect against, or to treat, gastrointestinal infection.
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