THE ENIGMATIC EOSINOPHIL - INVESTIGATION OF THE BIOLOGICAL ROLE OF EOSINOPHILS IN PARASITIC HELMINTH INFECTION

In many helminth infected hosts the number of eosinophils increases dr amatically, often without any concurrent increases in the number of ot her leukocytes, so that eosinophils become the dominant cell type. Man y experimental investigations have shown that the eosinophilia is indu ced by interleukin-5 (IL-5) but its functional significance remains un clear. Mice genetically deficient in IL-5 (IL-5-/-) have been used to evaluate the functional consequences of the IL-5 dependent eosinophili a in helminth infected hosts. Host pathology and level of infection we re determined in IL-5-/- and wild type mice infected with a range of s pecies representative of each major group of helminths; The effects of lL-5 deficiency were very heterogeneous. Of the six species of helmin th examined, IL-5 dependent immune responses had no detectable effect in infections with three species, namely the cestodes Mesocestoides co rti and Hymenolepis diminuta and the trematode Fasciola hepatica. In c ontrast, IL-5 dependent immune responses were functionally important i n mice infected with three species, notably all nematodes. Damage to t he lungs caused by migrating larvae of Toxocara canis was reduced in I L-5-/- mice. Infections of the intestine by adult stages of either Str ongyloides ratti or Heligmosomoides polygyrus were more severe in IL-5 -/- mice. Adult intestinal nematodes were clearly deleteriously affect ed by IL-5 dependent processes since in its presence there were fewer worms which had reduced fecundity and longevity. The implications of t hese results for the viability of using inhibitors of lL-5 as a therap y for asthma are considered.