CYTOKINE REGULATION OF HOST-DEFENSE AGAINST PARASITIC GASTROINTESTINAL NEMATODES - LESSONS FROM STUDIES WITH RODENT MODELS

Studies with rodents infected with Trichinella spiralis, Heligmosomoid es polygyrus, Nippostrongylus brasiliensis, and Trichuris muris have p rovided considerable information about immune mechanisms that protect against parasitic gastrointestinal nematodes. Four generalizations can be made: 1. CD4(+) T cells are critical for host protection; 2. IL-12 and IFN-gamma inhibit protective immunity; 3. IL-4 can: (a) be requir ed for host protection, (b) limit severity of infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines that are stere otypically produced in response to gastrointestinal nematode infection s fail to enhance host protection against some of the parasites that e licit their production. Host protection is redundant at two levels: 1. IL-4 has multiple effects on the immune system and on gut physiology (discussed in this review), more than one of which may protect against a particular parasite; and 2. IL-4 is often only one of multiple stim uli that can induce protection. Hosts may have evolved the ability to recognize features that characterize parasitic gastrointestinal nemato des as a class as triggers for a stereotypic cytokine response, but no t the ability to distinguish features of individual parasites as stimu li for more specific protective cytokine responses. As a result, hosts deploy a set of defense mechanisms against these parasites that toget her control infection by most members of that class, even though a spe cific defense mechanism may not be required to defend against a partic ular parasite and may even damage a host infected with that parasite.