EARLY CYTOKINE RESPONSES DURING INTESTINAL PARASITIC INFECTIONS

Infections with gastro-intestinal nematodes elicit immune and inflamma tory responses mediated by cytokines released from T-helper type-2 (Th 2) cells. In vitro assays of cells from the mesenteric lymph nodes (ML N) of experimentally infected rodents confirm that, after about 1 week , the dominant cytokine responses to mitogens and antigens are those a ssociated with this Th-cell subset. Polarization of the Th response in this way implies an initial local cytokine enviroment that favours Th 2 development. However, experimental infections with Trichinella spira lis and Nippostrongylus brasiliensis show that, within 2 days of worms reaching the intestine, MLN cells (MLNC) respond with a Th1 rather th an a Th2 response [i.e. there is an increase in mRNA for the type 1 cy tokine interferon-gamma (IFN-gamma), and mitogen-stimulated MLNC relea se IFN-gamma rather than interleukin-5 (IL-5)]. Antigen stimulation at this time does not elicit IFN-gamma release and the MLNC cannot adopt ively transfer immunity. Within a few days the MLNC phenotype changes. There is a Th2 response (IL-5 release) to both mitogen and antigen st imulation and MLNC can adoptively transfer immunity. Early release of IFN-gamma is T-cell dependent, with CD4(+) T cells playing the major r ole. The data are discussed in relation to factors regulating the muco sal response to invasion by parasites.