IL-4 treatment can cure established gastrointestinal nematode infections in immunocompetent and immunodeficient mice.
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 to 20 micrograms every 3 to 4 days, rapidly decreased egg production and, over a period of 6 to 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 severe combined immunodeficient (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 administrated when parasites were in larval stages than if administered after adult worms had developed. The effects of IL-4 were inhibited completely by an 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.
Urban
J F
JF
Helminthic Disease Laboratory, U.S. Department of Agriculture, Beltsville, MD 20705, USA.
Maliszewski
C R
CR
Madden
K B
KB
Katona
I M
IM
Finkelman
F D
FD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002452:Cell Count; D005260:Female; D005767:Gastrointestinal Diseases / Q000469:parasitology / Q000628:therapy; D015847:Interleukin-4 / Q000276:immunology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009351:Nematospiroides dubius / Q000276:immunology*; D009559:Nippostrongylus / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology; D019948:Receptors, Interleukin-4; D017206:Strongylida Infections / Q000628:therapy*
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4