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,
*
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307;
Division of Immunology, Department of Medicine, University of Cincinnati, Cincinnati, OH 45267;
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and
¶ Immunology and Disease Resistance Laboratory, Animal and Natural Resources Institute, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
The opinions and assertions in this article are those of the authors and do not necessarily represent those of the Department of Defense.
IL-4 and IL-13 promote gastrointestinal worm expulsion, at least in
part, through effects on nonlymphoid cells, such as intestinal
epithelial cells. The role of IL-4/IL-13 in the regulation of
intestinal epithelial function during Heligmosomoides
polygyrus (Hp) infection was investigated in
BALB/c mice infected with Hp or treated with a
long-lasting formulation of recombinant mouse IL-4/
IL-4
complexes (IL-4C) for 7 days. Separate groups of BALB/c mice
were drug-cured of initial infection and later reinfected and treated
with anti-IL-4R mAb, an antagonist of IL-4 and IL-13 receptor
binding, or with a control mAb. Segments of jejunum were mounted in
Ussing chambers, and short circuit current responses to acetylcholine,
histamine, serotonin, PGE2, and glucose were determined.
Although only modest changes in epithelial cell function were observed
during primary Hp infection, IL-4C or a secondary
Hp infection each induced more dramatic changes,
including increased mucosal permeability, reduced sodium-linked glucose
absorption, and increased Cl- secretory response to
PGE2. Some, but not all, effects of IL-4C and
Hp infection were dependent on enteric nerves.
Hp-induced changes in epithelial function were
attenuated or prevented by anti-IL-4R mAb. Thus, IL-4/IL-13 mediate
many of the effects of Hp infection on intestinal
epithelial cell function and do so both through direct effects on
epithelial cells and through indirect, enteric nerve-mediated
prosecretory effects. These immune system-independent effector
functions of IL-4/IL-13 may be important for host protection against
gastrointestinal nematodes.
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