Basic nutritional investigation
Abrogation of the oral tolerance to ovalbumin in mice by citrus pectin
Daria S. Khramova, M.Sc., Sergey V. Popov, Ph.D.*, Viktoria V. Golovchenko, Ph.D.,
Feodor V. Vityazev, M.Sc., Nikita M. Paderin, M.Sc., and Yury S. Ovodov, Prof. Dr.
Institute of Physiology, Komi Science Centre, The Urals Branch of the Russian Academy of Sciences, Syktyvkar, Republic of Komi, Russia
Manuscript received June 11, 2008; accepted August 25, 2008.
Abstract Objective: We studied the effects of dietary pectins (citrus pectin [CP] and apple pectin) on oral
tolerance in mice.
Methods: Pectins (1 mg/d) were administered orally for 2 wk. Tolerance was induced with 20 mg
of ovalbumin (OVA). Levels of serum antibodies (immunoglobulin [Ig] G, IgG1, IgG2a, IgE) and
delayed type hypersensitivity response determined in footpad tests were measured after subcutane-
ous injection of OVA with complete Freund’s adjuvant. Concentrations of immunoreactive OVA in
blood were measured by enzyme-linked immunosorbent assay after feeding the animals 20 mg of
OVA. Adhesion and cytokine production (tumor necrosis factor-, interferon-) were measured in
peritoneal macrophages.
Results: Oral administration of CP was found to prevent the induction of immune hyporespon-
siveness induced by OVA feeding. Animals fed OVA and CP were found to produce similar titers
of antigen-specific serum IgG and levels of delayed type hypersensitivity response as those animals
not fed OVA. CP increased levels of serum IgG1 and IgE. CP was found to enhance the penetration
of immunogenic OVA into the serum. CP (1 mg/d) administered orally for 1 wk was also observed
to enhance the adhesion and production of cytokines (tumor necrosis factor-, interferon-) in
peritoneal macrophages.
Conclusion: CP administered orally was shown to inhibit oral tolerance. Enhancement of protein
antigen penetration to the blood and activation of macrophages were found to precede the inhibitory
effect and appeared to mediate it. © 2009 Elsevier Inc. All rights reserved.
Keywords: Pectins; Citrus pectin; Oral tolerance; Ovalbumin; Anti-ovalbumin antibodies; Peritoneal macrophages; In-
flammatory cytokines; Adhesion
Introduction
Oral tolerance (OT) has long been recognized as a phys-
iologic mechanism of immune unresponsiveness to dietary
and bacterial antigens that maintain tissue integrity. Break-
down of OT may be the underlying cause of different
food-sensitive enteropathies and inflammatory bowel dis-
ease [1]. Therefore, the identification of factors that are able
to regulate OT is of great interest. It has been hypothesized
that food components may affect the immunogenic potential
of ingested proteins [2].
Pectic polysaccharides, which are major constituents in
the plant cell wall, are present in the diet and are widely
used in the food industry as gelling agents. Moreover, pec-
tins have been shown to possess some immunomodulatory
activity [3] and an ability to influence nutrient absorption
[4]. Oral administration of the polysaccharide fraction of a
dried extract (TJ-48) of the Japanese herb kampo to mice
resulted in changes in the intestinal immune system [5].
Furthermore, an acidic polysaccharide fraction prepared
from a constituent herb of juzen-taiho-to has been shown to
have protective activity against Candida infection in mice
[6]. Continuous feeding of the pectin bupleuran, which was
prepared from the roots of Bupleurum falcatum L., led to
enhancement of proliferation of spleen cells [7].
This work was supported by a grant from the Presidium of the Russian
Academy of Science (molecular and cellular biology), by the Russian Fund
for Basic Research (grant 06-04-48079), by the Ministry of Science and
Education (grant 02.512.11.2190), and by the Program for Leading Scien-
tific Schools.
* Corresponding author: Tel./fax: +7-8212-241001.
E-mail address: popov@physiol.komisc.ru (S. V. Popov).
Nutrition 25 (2009) 226 –232
www.elsevier.com/locate/nut
0899-9007/09/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.nut.2008.08.004