Chemistry Reference
In-Depth Information
to carry out its genuine functions in animal models,
reports showing a significant clinical effect of metal
exposure on the immune function in humans are
relatively uncommon and often of uncertain signifi-
cance. One explanation might be that early animal
studies often used high doses that may never or
only very rarely be relevant for the human situa-
tion. Even when more realistic doses were used in
the animal studies, the reserve capacity and redun-
dancy of the human immune system compared with
animals (Cunningham, 2002) might prevent any
clinical consequence. However, concurrent condi-
tions like malnutrition or chronic infections may
theoretically narrow the reserve capacity, allowing
metals to have a clinical immunosuppressive effect
that would not have developed in otherwise healthy
individuals. However, data on this subject are not
available.
and B cells (Wang
et al.,
1997), as well as hypersensi-
tivity (Sections 5.2 and 5.3).
4 HYPERSENSITIVITY INDUCED
BY METALS
4.1 General Considerations
Several metals may interact with the immune sys-
tem causing a specifi c immune activation that damages
the tissues of the body; the response is exaggerated
and/or inappropriate in relation to the situation. The
mechanisms involved in these hypersensitivity reac-
tions were classifi ed as type I-IV by Coombs and Gell
in 1968. Although this classifi cation has been criti-
cized for not taking into account recent progress in the
understanding of the immune system and reactions to
xenobiotica, especially drugs (Descotes and Choquet-
Kastylevsky, 2001), it is still widely used. However,
it does not indicate the involvement of T cells in the
induction of hypersensitivity reactions described as
antibody-mediated in the classifi cation (type II and
III). Furthermore, it does not take into account so-
called pseudoallergic (anaphylactoid) reactions, where
xenobiotics activate complement or release mediators
such as histamine without involvement of antibodies.
Finally, a xenobiotic may well cause hypersensitivity
by more than one mechanism in the individual patient
and over time (Descotes and Choquet-Kastylevsky,
2001). Keeping these important comments in mind,
the following description will follow the traditional
Coombs and Gell classifi cation.
3 ESSENTIAL METALS AND
THE IMMUNE SYSTEM
The elements zinc, iron, copper, selenium, chro-
mium, and cobalt are essential metals for the human
body and the immune system. There is ample evi-
dence that Fe defi ciency comprises humoral immu-
nity in both humans (Feng
et al.,
1994; MacDougall
and Jacobs, 1978) and animals (Kochanowski and
Sherman, 1985), possibly because of the need for
iron in early events associated with cell activation,
including generation of second messengers (Kuvibi-
dila
et al.,
1999). In contrast, excess iron suppresses
innate and cell-mediated immunity (Bowlus, 2003).
Zn defi ciency and the following increased corticos-
teroid levels cause apoptotic loss of precursor B and
T cells in mice, leading to thymic atrophy and lym-
phopenia (Fraker and King, 2004). Zn defi ciency also
seems to be of clinical relevance in humans (Black,
2003). Excess of Zn has resulted in divergent effects
on the immune function, including some reports of
immunostimulation in humans. Copper defi ciency
is immunosuppressive and reduces IL-2 and T-cell
proliferation (Percival, 1998), whereas an excess
of copper seems to be of little importance for the
immune system. Selenium has a benefi cial effect
on the immune function, strengthening primarily
the cell-mediated immunity by upregulating the
expression of the T-cell high-affi nity IL-2 receptor
(Kiremidjian-Schumacher and Stotzky, 1987) and, as
a consequence, also stimulating antibody production
(Hawkes
et al.,
2001). Chromium (Anderson, 2000)
and cobalt (Barceloux, 1999) are essentials metals but
may cause suppression of T cells (Faleiro
et al.,
1996)
4.2 Type I Hypersensitivity (Anaphylactic
or Immediate Hypersensitivity)
In IgE-mediated hypersensitivity, the immune sys-
tem has become sensitized to certain substances—
allergens—and will on renewed exposure to these
substances elicit a release reaction from mast cells
armed with the allergen-specifi c IgE antibodies. The
release of vasoactive amines (histamines, leukotrienes,
platelet-activating factor), together with eosinophilic
and neutrophilic chemotactic factors, is responsible
for the clinical manifestations such as hay fever with
rhinitis and conjunctivitis, asthma, and the calami-
tous systemic anaphylactic reaction. Symptoms of this
type have been recognized since the 19th century after
exposure to platinum compounds, now recognized to
be platinum salts containing reactive halogen ligands
(Merget
et al.,
1988). Induction of asthma by chromium
and nickel compounds has also been described (Haines
and Nieboer, 1988; Novey
et al.,
1983).
