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Title: BOTH IL-4 AND IL-13 MEDIATE THE EXPULSION OF GASTROINTESTINAL NEMATODE PARASITE THROUGH AN IL-4RA CHAIN AND STAT6-DEPENDENT

Author
item Urban, Joseph
item NOBEN-TRAUTH, NANCY - NIAID, NIH, BETHESDA, MD
item DONALDSON, DEBRA - GENETICS INST, MA
item MADDEN, KATHLEEN - USUHS, BETHESDA, MD
item MORRIS, SUZANNE - UN CINCINNATI, OH
item COLLINS, MARY - GENETICS INST, MA
item FINKELMANN, FRED - UN CINCINNATI, OH

Submitted to: Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: We have demonstrated that a naturally occurring molecule called interleukin-4 (IL-4) is produced by animals and is able to induce the expulsion of worm parasites from the intestine. IL-4 can be used as an adjunct or replacement therapy for chemical control of infections in livestock that often require withdrawal time before meat can be consumed by ythe public. Knowledge of how IL-4 is stimulated to appear during an infection would be useful for designing procedures that enhance its induction during an infection or can be used to design synthetic molecules that mimic the effects of this molecule. This study shows that another unique molecule, called IL-13, is also stimulated by certain parasite infections. It is not clear if the combination of IL-4 and IL-13 are more effective than either alone or whether their effects are relevant to only certain kinds of parasite infection. Scientists will be able to use this information to target the stimulation of these molecules during an infection or as a preventative measure for livestock or humans that are at risk of being infected by worm parasites.

Technical Abstract: Although IL-4 induces expulsion of the gastrointestinal nematode parasite, Nippostrongylus brasiliensis (Nb), from immunodeficient mice, this parasite is expelled normally by IL-4-deficient mice. This apparent paradox is explained by observations that: 1) IL-4 receptor à chain (IL-4Rà)-deficient mice and STAT6-deficient mice fail to expel Nb; and 2) a specific antagonist for IL-13, another activator of STAT6 through IL-4Rà, inhibits worm expulsion. Thus, either IL-4 or IL-13 can induce Nb expulsion via IL- 4Rà and STAT6, and IL-13 may be a more important inducer of spontaneous expulsion that IL-4. Additional observations made in the course of these experiments demonstrate that STAT6 signalling is not required for IL-4 enhancement of IgG1 production and actually inhibits IL-4-induction of mucosal mastocytosis.