Local intestinal immune responses to infections with Trichinella spiralis. Real-time, continuous assay of cytokines in the intestinal (afferent) and efferent thoracic duct lymph of rats

Levels of IL-4, IL-5, TNF-alpha, and IFN-gamma were quantitated in the intestinal (afferent) and efferent thoracic duct lymph of rats during the course (0 to 289 h) of an infection with Trichinella spiralis. Intestinal lymph was collected by cannulating thoracic ducts of mesenteric lymphadenectomized animals. These studies showed that cytokines typical of a Th2 type (IL-4 and IL-5) and a Th1 type (IFN-gamma) were simultaneously detected in the intestinal lymph during the first 8 days after infection. Worm expulsion (day 11 to 12) was associated with increased levels of IL-4 and IL-5 in the intestinal lymph. IL-5 levels rose as early as 15 to 20 h and remained elevated throughout the infection. IL-4 activity appeared in intestinal lymph 60 h after infection and reached peak levels during worm expulsion. Despite the predominantly Th2 nature of cytokine response, IFN-gamma levels showed several cycles of high and low production during the course of infection. A comparison of cytokine levels between intestinal and efferent lymph values showed no significant differences in IL-4 or IL-5 levels suggesting no contribution by the mesenteric node to efferent lymph. However, IFN-gamma and TNF-alpha levels were lower in efferent lymph compared with intestinal lymph suggesting mesenteric node consumption. Adoptive transfer experiments showed that protective CD4+CD45RC- cells primed the gut for a more rapid TH2-type response that was faster than in a primary infection. In contrast, adoptive transfer of CD4+CD45RC+ cells primed the gut for a more rapid Th1-type(IFN-gamma) response. These studies demonstrate a novel method for measuring real-time changes in cytokine levels in the gut during the course of an active infection.