Antioxidant Nutrients and Immune Functions

172 Pages·1990·31.83 MB·English

by  Adrianne Bendich (auth.)

ANTIOXIDANT
NUTRIENTS AND
IMMUNE FUNCTIONS
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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ANTIOXIDANT NUTRIENTS AND IMMUNE FUNCTIONS
Edited by Adrianne Bendich, Marshall Phillips, and Robert P. Tengerdy
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ANTIOXIDANT
NUTRIENTS AND
IMMUNE FUNCTIONS
Edited by
Adrianne Bendich
Hoffmann LaRoche, Inc.
Nutley, New Jersey
Marshall Phillips
Agricultural Research Service, USDA, NADC
Ames, Iowa
and
Robert P. Tengerdy
Colorado State University
Fort Collins, Colorado
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Agricultural and Food Chemistry Division of the American Chemical Society Sym
posium on Antioxidant Nutrients and the Immune Response (1988: Los Angeles, Calif.)
Antioxidant nutrients and immune functions / edited by Adrianne Bendich, Mar
shall Phillips, Robert P. Tengerdy.
p. cm. -(Advances in experimental medicine and biology; v. 262)
Includes bibliographical references.
ISBN-13: 978-1-4612-7863-4 e-ISBN-13: 978-1-4613-0553-8
DOl: 10.1007/978-1-4613-0553-8
1. Immunity-Nutritional aspects-Congresses. 2. Antioxidants-Physiological ef
fect-Congresses. 3. Active oxygen-Physiological effect-Congresses. I. Bendich,
Adrianne. II. Phillips, Marshall. III. Tengerdy, Robert P. IV. American Chemical
Society. Division of Agricultural and Food Chemistry. V. Title. VI. Series.
QRI85.2.A36 1988 89-26570
599'.029-dc20 CIP
Proceedings of the Agricultural and Food Chemistry Division of
the American Chemical Society Symposium on Antioxidant Nutrients
and the Immune Response, held September 29, 1988,
in Los Angeles, California
© 1990 Plenum Press, New York
Softcover reprint of the hardcover I st edition 1990
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Adrianne Bendich dedicates this book to:
David, Jorden, and Debra,
Joseph, Lillian, and Elaine
Marshall Phillips dedicates this book to:
Karen, Tacy, Dori, and Larry
Robert Tengerdy dedicates this book to:
Katherine, Thomas, and Peter
PREFACE
The detenmnation of optimal nutritional status has traditionally been based upon
generalized parameters such as weight gain and body fat levels. Vitamin and mineral
requirements were often related to the intakes needed to prevent overt signs of deficiency
diseases such as beriberi or scurvy. However, in the past decade or so, there have been
intensive investigations to determine the subtle changes in physiological functions
associated with marginal micronutrient intakes. There is a growing consensus that immune
system activities are very sensitive indicators of micronutrient status. During this decade,
there has also been a rapid expansion of research in the role of free radicals and
antioxidants in the major chronic diseases which afflict mankind( i.e. cancer,
cardiovascular disease,and autoimmune disease).
The main function of antioxidant nutrients in an appropriate diet is the prevention of
oxidative damage to cells and their physiological functions. Antioxidant nutrients
counteract free radicals and damaging oxidative actions on cell membranes. Since the cells
of the immune system are rapidly differentiating and proliferating, such dividing and
transforming cells are particularly susceptible to damage by oxidation.
The interactions of antioxidant nutrition and immune system activities and disease
resistance are therefore logical areas for research. Thus, the objective of this symposium
was to bring together the leading investigators who have examined the immunological
effects of dietary essential nutrients which share the capacity to act as antioxidants.
Over the past 15 years, there has been a growing interest in the reproducible
adverse effects of the deficiencies of vitamins C and E, zinc, selenium or copper deficiency
of cellular and humoral responses as well as phagocytic function. Oxidative damage to
leukocytes and immunosuppressive effects of prostaglandin E 2, lipid peroxides and
conjugated immunoglobulins are possible rationales for immunosuppression associated
with antioxidant micronutrient deficiencies. Similarly, many studies have also found
immunoenhancement associated with dietary supplementation of the above micronutrients
as well as with beta carotene.
Sound nutrition consists of a necessary balance between the various elements of the
diet: protein, calories, lipids, vitamins and minerals. The nutritional state of individuals
may be a clue that determines immunocompetence and disease resistance.The interest in
proper nutrition has moved beyond the scientific laboratory and has reached into the public
awareness. The perception of the health consequences of sound nutrition is as important as
the scientific validity. Therefore, it is anticipated that the research from the emerging field
of nutritional immunology will be seriously considered in the development of nutrition
policy. Because of the importance of antioxidant nutritional status and its effects on
immunocompetence, further research is recommended with emphasis on clinical and
epidemiological areas.
Adrianne Bendich
Marshall Phillips
Robert Tengerdy
vii
ACKNOWLEDGEMENTS
The authors acknowledge the Division of Agricultural and Food Chemistry of the American
Chemical Society for sponsoring this symposium at the National meeting in Los Angeles.
Financial contributions and support from Hoffman-LaRoche, Inc., Mead Johnson
Nutritional Division, Nabisco Brands, Inc., Quaker Oats Company, and Takeda U.S.A.,
Inc., are sincerely acknowledged.
We appreciate the technical assistance of Ms. Janice Olson whose dedication to the
production of this book is greatly appreciated.
ix
CONTENTS
Introduction -Antioxidant Nutrients and Immune Functions. . . . . . . . . . . . . . . . . 1
ABendich
Cellular and Molecular Basis of Nutrition-Immunity Interactions. . . . . . . . . . . . .. 13
R.K. Chandra
The Role of Antioxidants in Modulating Neutrophil Functional Responses. . . . . .. 19
L.A Boxer
Antioxidant Vitamins and Their Functions in Immune Responses ............. 35
A Bendich
Antioxidants and the Aging Immune Response. . . . . . . . . . . . . . . . . . . . . . . . .. 57
S.N. Meydani, M.Meydani, and J.B. Blumberg
Anti-inflammatory Systems in Human Milk. . . . . . . . . . . . . . . . . . . . . . . . . . .. 69
AS. Goldman, Randall M. Goldblum, and Lars A Hanson
The Administration of Beta Carotene to Prevent and Regress Oral Carcinoma
in the Hamster Cheek Pouch and the Associated Enhancement of the Immune
Response .............................................. 77
J.L. Schwartz, G.Shklar, E.Flynn, and D.Trickler
Studies on Membrane Lipid Peroxidation in Omega-3 Fatty Acid-Fed
Autoimmune Mice: Effect of Vitamin E Supplementation ......... . . . .. 95
S.Laganiere, B.P.Yu, and G.Fernandes
Immunity and Disease Resistance in Farm Animals Fed Vitamin E Supplement . . .. 103
R.P. Tengerdy
Possible Roles for Zinc in Destruction of Tryparwsoma cruzi by Toxic
Oxygen Metabolites Produced by Mononuclear Phagocytes . . . . . . . . . . . .. 111
J.M. Cook-Mills, J.J. Wirth, and P.l Fraker
Effects of Copper Deficiency on the Immune System. . . . . . . . . . . . . . . . . . . . .. 123
J.R. Prohaska and O.A Lukasewycz
Selenium and Glutathione Peroxidase: Essential Nutrient and Antioxidant
Component of the Immune System ............................. 145
J.E. Spallholz
Epilogue .................................................... 159
R.P. Tengerdy
Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Index ...................................................... 165
xi
ANTIOXIDANT NUTRIENTS AND IMMUNE FUNCTIONS -INTRODUCTION
Adrianne Bendich
Clinical Research Coordinator
Hoffmann-LaRoche Inc.
340 Kingsland St.
Nutley, N.J.
INTRODUCTION
The purpose of this chapter is to examine the role of antioxidants, and thus the role of free
radicals in the activities of the immune system. The chapter is divided into three main sections,
free radicals, antioxidants and an introduction to the activities of the immune system, especially
those involving oxidative reactions. The information presented by each symposium speaker is
highlighted in this introduction so that the reader can refer to the appropriate chapter for more
detailed information.
FREE RADICALS
Chemical compounds contain two or more elements that are bound together by a chemical
bond In most instances, the bonding involves negatively-charged electrons. The arrangement
of the electrons determine the stability of the compound. A stable compound has electrons that
are paired. If an electron is unpaired, the molecule becomes more reactive and unstable than the
parent compound (Dormandy, 1983). A compound or element with one or more unpaired
electrons is called a free radical.
In order to stabilize itself, the free radical abstracts an electron from a stable compound
which, in turn, is transformed into a new free radical. This chain reaction will continue until the
free radical containing the lone electron pairs up with another molecule with an unpaired
electron, or is deactivated by a chain reaction-breaking antioxidant. There are also certain free
radical scavengers and enzymes which can facilitate the decomposition of reactive molecules
which are precursors of free radicals. These compounds can therefore lower the free radical
burden before a chain reaction begins (Grisham and McCord, 1986; Sies, 1985).
Oxygen containing reactive molecules (some of which are free radicals) are the most
critical to biological systems. Since oxygen is required for cell viability, it is essential that
mechanisms ~ available to control the reactive oxygen intermediates generated during cellular
respiration. As seen in Fig 1, there are three major reactions of oxygen which result in the
formation of oxygen species more reactive than molecular oxygen.
When oxygen is exposed to a source of high energy such as ultraviolet light, the energy is
transferred to form singlet oxygen (reaction 1). Singlet oxygen still contains a pair of electrons
and cannot be classified as a free radical. However, these two electrons exist in an unstable
conformation in the molecule and thus the potential exists for this molecule to participate in
reactions that generate free radicals. One example of a free radical produced through singlet
oxygen reactions is the superoxide radical. Singlet oxygen can be deactivated, thereby
A. Bendich et al. (eds.), Antioxidant Nutrients and Immune Functions
© Plenum Press, New York 1990
preventing the formation of the superoxide radical. This process is called singlet oxygen
quenching «(Halliwell and Gutteridge, 1985). The quencher dissipates energy contained in the
singlet oxygen molecule. As a result, it lacks the energy to engage in superoxide-producing
reactions. The most effective, naturally-occurring singlet oxygen quencher is beta-carotene
(Krinsky and Deneke, 1982).
° .
1) 02 + energy (singlet oxygen)
2
------_._.~ 2 H20 (mitochondrial electron
transport system)
°
3a) 02 + e ________I I.~ 2• - (superoxide radical anion)
_______
-II.~ 02 + H202 (hydrogen peroxide)
---_._~ 02 + H20 + HO· (hydroxyl radical)
Fig. 1. Reactions with oxygen resulting in more reactive species than oxygen.
Over 98% of oxygen utilized by cells is efficiently reduced by the electron transport
system (reaction 2). However the remaining oxygen is available for one or two electron
reduction, resulting in the formation of the superoxide radical (reaction 3a) and hydrogen
peroxide (reaction 3b or 3c). These two products can react to form water, however, in the
process, the highly reactive hydroxyl radical is generated (3d). Electron transport systems are
thus prime, continuous sources of intracellular, reactive oxygenated free radicals. In addition,
electron transfer from the superoxide radical to transition metals such as iron also generates
hydroxyl radicals (Grisham & McCord, 1986).
The cellular sites of free radical generation include mitochondria, lysosomes,
peroxisomes, nuclear, endoplasmic reticular and plasma membranes. Free radicals and their
products are also present within the cytosol. Molecular species include, but by no means are
limited to hydroxyl, peroxy, hypochlorite, superoxide and alkoxy radicals and reactive
molecules such as hydrogen peroxide and singlet oxygen, which are not free radicals but are
certainly reactive and capable of causing damage (Machlin and Bendich, 1987).
Prime targets for free radical reactions are the unsaturated bonds in the lipids found in all
cellular membranes. Consequently, there is loss of membrane fluidity, receptor alignment and
potentially cellular lysis. Free radical damage to the sulfur containing enzymes and other
proteins results in inactivation, cross-linking and denaturation. Nucleic acids can be attacked
and subsequent damage to the DNA can cause mutations which may be carcinogenic. Oxidative
damage to carbohydrates can alter any of the cellular receptor functions including those
associated with interleukin activities and prostaglandin formation. Examples of tissue and
organ damage associated with free radical reactions include the destruction of endothelial cells
which line the blood vessels and consequent macrophage invasion (Halliwell and Gutteridge,
1985; Flohe et al., 1985; Gey et al., 1987), the inflammatory response seen in arthritic joints
(Hirschelmann and Bekemeier, 1981; Slater, 1972), the hastening of the aging process (Cutler,
1986), and the destruction of lung tissue (Freeman and Crapo, 1982).
Endogenous sources of oxygen-containing free radicals include those generated
intracellularly as well as those that are formed within the cell and released into the surrounding
area. Intracellular free radicals are generated from the autooxidation and consequent inactivation
of small molecules such as thiols and catecholamines, the activity of certain oxidases,
2