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Title: IL-4 CURES ESTABLISHED NEMATODE INFECTIONS

Author
item URBAN JOSEPH F - 1265-20-00
item MALISZEWSKI CHAR - UNIFORMED SERVICES UNIV
item MADDEN KATHLEEN - UNIFORMED SERVICES UNIV
item KATONA ILDY M - UNIFORMED SERVICES UNIV
item FINKELMAN FRED D - UNIFORMED SERVICES UNIV

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Immune cells produce instructional molecules called cytokines that can expand specific immune responses as well as direct non-specific aspects of inflammation. Interleukin-4 (IL-4) is a cytokine that has been associated with the immune response to parasitic infection. The clearance of gastrointestinal nematode worm parasites from infected normal and immunodeficient animals is the first demonstration of a therapeutic role for IL-4 in a worm infection exclusive of immune cells. This observation will be beneficial to control of worm infections in livestock when IL-4, which is present in higher animals, is produced.

Technical Abstract: We examined the ability of a long-acting formulation of IL-4 (IL- 4/anti-IL-4 mAB complexes) to limit established infections of normal and immune-deficient mice with two nematode parasites: Heligmosomoides polygyrus and Nippostrongylus brasiliensis. IL-4, at a dose of 5-20 ug every 3-4 days, rapidly decreased egg production and, over a period of 6-9 days, terminated infection in H. polygyrus-inoculated BALB/c mice. IL-4 treatment also considerably decreased egg production in H. polygyrus-inoculated CB.17 SCID mice and terminated infection in N. brasiliensis- inoculated SCID mice and anti-CD4 mAB-treated BALB/c mice. IL-4 was less effective at limiting H. polygyrus infection if administered when parasites were in larval stages than if administered after adult worms had developed. The effects of IL-4 were completely inhibited by a mAB that specifically blocks the mouse IL-4R. These observations demonstrate that IL-4 can limit the fecundity and survival of gastrointestinal nematode parasites through effects on the host that are independent of the specific immune system.