Submitted to: Gastroenterology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 13, 1997
Publication Date: N/A
Interpretive Summary: Infections with worm parasites evoke characteristic responses by the host. One such effect is expulsion of the worm. Induction of the expulsion mechanism during an infection is an extremely effective way of curing the host of the worm without causing disease. Knowledge of how this mechanism works would allow scientists to duplicate the response in ways that could be useful for the control of worm infections in humans and livestock. We have made the observation that a particular host-derived molecule called IL-4 is able to induce expulsion of a worm infection. This is an important discovery because it attributes the very complex intestinal expulsion response to a single molecule. The activity of this molecule seems to be directed primarily at epithelial cells that line the intestine and regulate normal absorption and secretion in the gut. The effectiveness of this natural molecule could be mimicked by pharmaceutical company scientists to produce a product that could be used to clear infections in humans and livestock. This approach would be an adjunct to other methods of control or could replace chemical control procedures that often require withdrawal times before livestock can be processed for consumption. This approach would be more compatible with food safety concerns felt by the public.
IL-4 is an antiinflammatory cytokine important in the differentiation of T cells into type 2 cytokine-secreting cells that characterize nematode infection. The role of IL-4 in the regulation of epithelial function during Heligmosomoides polygyrus (Hp) infection was investigated. Mice were treated with IL-4 for 1 or 7 days, were infected with Hp, or given IL- -4 for 1 day after Hp infection. Other mice were cured of the initial infection, then reinfected and treated with an anti-IL-4 receptor(R) antibody (mAb). Segments of the jejunum were mounted in Ussing chambers and changes in Isc were determined for acetylcholine, histamine, prostaglandin E2 or glucose. The Hp infection had little effect on epithelial cell responses while both secretion and absorption were altered in reinfected mice. Several changers in epithelial cell function observed in reinfected mice were blocked by anti-IL-4R mAb or were induced in uninfected mice by treatment with IL-4. The IL-4 alone decreased barrier function, but increased secretion in response to inflammatory mediators. These effects were observed at 7 days, but not 1 day after treatment with IL-4. IL-4 mediates several of the effects of Hp infection on intestinal epithelial cell function: it has direct effects on the epithelial cell as well as indirect prosecretory effects via mast cells, and it contributes to host defense by altering cellular function to adversely affect nematode survival.