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6.4 Meaningfulness of Immune Biomarkers in Relation
to Individual and Population Health
As aforementioned, several biomarkers of the immune response (immunomarkers) are
shared among vertebrates and, to a lesser extent, with invertebrates (Fournier et al. 2000a;
Kouassi et al. 2003). These immunomarkers can be affected by xenobiotics such as drugs
and pollutant chemicals (Brousseau et al. 1997a, 1997b; Fournier et al. 2000a, 2000b).
However, effects on immune functions do not necessarily imply an impact on host resis-
tance to pathogens or an increased susceptibility to cancer. Environmental doses and
ways of exposure are important factors to take into account to address the relevance of the
effect on immunomarkers in terms of risk assessment analysis. As with other systems, the
immune system has a great “plasticity,” and effects at lower levels of biological organiza-
tion (molecular and cellular) have to overcome detoxification and compensation processes
before they affect higher levels of organization (tissue and organism).
Immunotoxic effects of xenobiotics have been reported in every major immune tissue
in vertebrates, including bone marrow, thymus, spleen, and lymph nodes. Effects at cel-
lular level have also been characterized. Xenobiotics can strongly impair the functions
of macrophages, monocytes, or B and T cells with impacts on the nonspecific immune
response as well as on the humoral and cell-mediated immune response (Kouassi et al.
2003; Fournier et al. 2000a; Brousseau et al. 1997a). These effects can result in immu-
nodepression or immunostimulation, leading to hypersensitivity and autoimmunity
disorders.
Immunodepression can result in a decrease of host resistance to parasite or viral and
bacterial infections, and as previously described, environmental exposure to immuno-
toxic chemicals has been pinpointed to explain the high mortality during several epizoot-
ics that affected marine mammal populations inhabiting highly polluted areas. Severe
immunodepression can be easily identified by histological alterations of lymphoid tis-
sues, immunophenotyping, and
ex vivo
functional assays. In contrast, moderate long-term
immunodepression is much more difficult to detect, and can lead to an increase of the
incidence of cancer.
Polybrominated biphenyls, PCBs, dioxins, furans, and organochlorinated insecticides
have been reported to induce immunodepression (Voccia et al. 1999). Trace metals (mer-
cury, cadmium, lead, etc.) have also been listed as immunotoxic compounds (Omara et al.
1998; Zelikoff and Thomas 1998). Exposure to these chemicals can generally result in an
increase of host susceptibility to bacterial or viral infections. However, given the complex-
ity and the specificity of the immune response, challenges against different types of patho-
gens have to be included in the risk assessment analysis of immunotoxic compounds.
In case of chemical contamination, immunostimulation is characterized by an aberrant
stimulation of the immune response. Different drugs and chemicals have been used to
qualitatively modify the immune response including interferon, interleukins, levamisole,
and dithiocarbamate derivatives (Haller 2001; Holcombe et al. 2001). Other compounds
including isoprinosine, muramyl dipeptide, azimexon, bestatin, tuftsin, and pyrimidinols
are strong immunostimulants and are known to shorten the disease period of several
infections (Hadden 1987). However, the beneficial effects of these compounds are gener-
ally counterbalanced by strong side effects such as induction of autoimmune disorders
(Krzystyniak et al. 1995; Kimber 2002). Although some trace metals have been demon-
strated to have potentiator effects at lower levels of exposure (Bernier et al. 1995), the
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