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. In testinal lymph was collected by cannulating thoracic ducts of mesenter ic lymphadenectomized animals, These studies showed that cytokines typ ical of a Th2 type (IL-4 and IL-5) and a Th1 type (IFN-gamma) were sim ultaneously detected in the intestinal lymph during the first 8 days a fter infection, Worm expulsion (day it to 12) was associated with incr eased levels of IL-4 and IL-5 in the intestinal lymph, IL-5 levels ros e as early as 15 to 20 h and remained elevated throughout the infectio n, 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 responses, IFN-gamma levels showed several cycl es of high and low production during the course of infection, A compar ison of cytokine levels between intestinal and efferent lymph values s howed no significant differences in IL-4 or IL-5 levels suggesting no contribution by the mesenteric node to efferent lymph, However, IFN-ga mma and TNF-alpha levels were lower in efferent lymph compared with in testinal lymph suggesting mesenteric node consumption. Adoptive transf er experiments showed that protective CD4(+)CD45RC(-) cells primed the gut for a Th2-type response that was faster than in a primary infecti on, In contrast, adoptive transfer of CD4(+)CD45RC(+) cells primed the gut for a more rapid Th1-type (IFN-gamma) response, These studies dem onstrate a novel method for measuring real-time changes in cytokine le vels in the gut during the course of an active infection.