|Finkelman, Fred - COLL MED CINCINNATI OH|
|Wynn, Thomas - NIH BETHESDA MD|
|Donaldson, Debra - GENET INST CAMBRIDGE MA|
Submitted to: Current Opinions in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 15, 1999
Publication Date: August 15, 1999
Citation: Finkelman, F.D., Wynn, T.A., Donaldson, D.D., Urban Jr, J.F. 1999. Il-13: role in helminth-induced inflammation and protective immunity against nematode infections. Current Opinions in Immunology. 11:420-426 (1999) Interpretive Summary: Infection of livestock with gastrointestinal (GI) nematode parasites is a significant economic concern to producers, and certain infections posse a threat to the safe ingestion of animal tissues by the public. The nature of the immune response to GI parasites is complex but vaccination is a desirable control strategy because it eliminates the risk of drug residues and can provide long-term protection. Basic studies on the mechanism of protective immunity to GI parasites reveal a more complete knowledge of the extracellular and intracellular events necessary for effective immunity. IL-13 is a recently discovered soluble regulatory protein that plays a role in the development of immunity to GI nematodes. However, it can also contributed to allergic diseases at mucus membranes when it is inappropriately activated. The current report discusses up to date information on the activities associated with IL-13 production, and presents conceptual aspects of the appropriate induction of IL-13 that minimizes harmful effects while enhancing its role in protective responses. This information will be of value to government, academic and industrial scientists that consider improvements in the development of effective vaccines against parasitic worms and the control of allergic diseases.
Technical Abstract: Helminth infections induce the production of type 2 cytokines that contribute both to expulsion of parasitic worms and inflammatory responses that can either protect or damage the host. While IL-4 has been considered the most critical cytokine for both inflammation and protective immunity, recent observations indicate that the related cytokine, IL-13, can have equal or even greater importance than IL-4 in inflammatory responses and host protection against gastrointestinal (GI) nematode infection. Studies performed in mice deficient in the IL-4Ralpha chain of the IL-4 receptor or its associated signaling molecule, Stat6, indicated that both IL-4 and IL-13 regulate protective responses to parasitic infections in the intestine. In addition, both IL-4 and IL-13 can act independently to induce protective immunity to a variety of GI nematode parasites that have different life cycles and inhabit different regions of the intestine. Potential mechanisms of IL-13-dependent immunity to nematode infections ar presented and the development of therapeutic interventions related to increases in IL-13 activity is discussed.