Food Lipids: Chemistry, Nutrition, and Biotechnology

done predominantly in rodent species with studies in humans. Macrophages are one
of the most important sources of eicosanoids in the body, playing a major role in a
variety of inflammatory and immunologic responses. Membranes of these cells are
particularly enriched with arachidonic acid. Different inflammatory stimuli have the
ability to induce secretion of eicosanoids of varied forms. Lymphocytes do not seem
able to produce eicosanoids but can release arachidonic acid and certainly respond
to the effects of these mediators. Many research studies describe use of mononuclear
cells—these are mixed populations of lymphocytes and monocytes, usually obtained
by differential centrifugation of blood or other biological fluids.
C. Eicosanoids and Immunity
Since eicosanoids are soluble mediators of the inflammatory response, their role is
critical in many types of immune reaction. One of the most widely used drugs in
the world, aspirin, is a cyclooxygenase inhibitor that reduces prostaglandin synthesis.
The anti-inflammatory effect of aspirin and other nonsteroidal anti-inflammatory
drugs (NSAIDs) is due to blocking of the metabolism of arachidonic acid by cyclooxygenase.
Some animal studies suggest that high doses of other prostaglandin
inhibitors, like indomethacin, may enhance some mononuclear cell dependent responses.
There are limited reports that humans with deficient immune responses
respond to indomethacin treatment whereas some normal individuals do not benefit
from treatment with this drug and others show an increase in certain antibody responses
[2]. The variation in response might be a function of which eicosanoid is
involved in the altered immune responses. Burn injury leads to elevations of prostaglandin
E and immune hyporesponsiveness. Administration of prostaglandin inhibitors
lowers the PGE levels and partially corrects the immune response. NSAID
administration appears to prevent colon cancer in both humans and experimental
animals; in addition, prostaglandin synthesis is decreased by these drugs. It is unknown
how these compounds inhibit the growth of colon cancer [3]. While there
may be direct effects of these prostaglandin inhibitors on several aspects of colon
carcinogenesis, including changes in cell metabolism, the cell cycle, and expression
of tumor suppressor proteins, one cannot rule out alterations in immune response.
D. Noneicosanoid Mediators
Although it is clear that dietary fatty acids exert powerful effects on eicosanoids,
which in turn profoundly modify some aspects of the immune response, alternate
mechanisms by which dietary fat can alter immune responses have been proposed.
These include changes in membrane microviscosity and dependent events, as well
as the direct activation of protein kinase C (PKC) by arachidonic acid. The role of
PKC is modulated by diacylglycerols (DAGs), whose affinity for PKC is altered by
changes in the fatty acid moieties on the DAGs. Other potential mechanisms that
have been implicated are activation of GTP-binding proteins by fatty acids and
changes in phospholipase activity in the cell membrane. Finally, increased oxidation
is suspected as one of the mediators of �3 fatty acid effects on immune cells; an
increase in dietary vitamin E that restored the in vitro responses of T cells from
subjects fed fish oil was interpreted as supporting the possibility of such mediating
activity [4]. Also, carotenoids exhibit both antioxidant and immunomodulatory roles
that may be related. Feeding of carotenoids raises the number of circulating lym-
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.