ABSTRACT
Topical exposure to a variety of xenobiotics may result in irritant contact
dermatitis (ICD) as well as allergic contact dermatitis (ACD), both in animals
and humans. ICD and ACD may have clinical, histological and immuno-
histochemical similarities (Lammintausta and Maibach, 1990; Patil and
Maibach, 1994; Brasch et al., 1992; Scheynius et al., 1984), but the immuno-
logical mechanisms that underlie both types of response are thought to be
essentially different. Allergic contact hypersensitivity has been considered
a prototype of cutaneous delayed-type hypersensitivity reaction, requiring the
activation and clonal expansion of allergen-responsive T-lymphocytes. The
cutaneous inflammatory response is thus orchestrated by primed memory
T-cells. In contrast, ICD has been defined as local inflammatory reaction
following a single or repeated exposure to an irritant, which is an agent
producing direct toxic insult to the cutaneous cells (Mathias and Maibach,
1978). Irritants are believed to initiate the immune cascade independently of
the antigen presentation pathway, by inducing proinflammatory mediators
that directly recruit and activate T-lymphocytes. Irritant reactions do not result
in the induction of antigen-specific memory T-cells, and are considered as
the result of a primarily nonimmunological damage to the skin. However, as
new information becomes available, the distinction between immunological
and nonimmunological events becomes progressively blurred, and it is now
apparent that allergic and irritant contact reactions have at least partially
overlapping pathophysiology and share common effector pathways (Brand
et al., 1996; Effendy et al., 2000; Mohamadzadeh et al., 1994). Moreover, many
chemicals that are capable of behaving as contact allergens have also irritant
properties, frequently disregarded because their allergenic potential dominates
their toxicity profile. Indeed, it is believed that irritancy promotes allergic
sensitization to some degree, even if the mechanisms underlying this interaction
are only partially known. The “danger signal” hypothesis (Matzinger, 1998)
suggests that the immune responses can be induced by danger signals released
by tissues undergoing stress, damage or abnormal death. In this context, an
antigenic signal will produce sensitization only in the presence of a danger
signal; in its absence tolerance will occur. Irritancy may represent a “danger
signal” for the immune system as direct toxic damage of dendritic cells (DC) or
other cells (principally keratinocytes) and cytokine release may activate the DC
and therefore, predispose to allergic sensitization (Gallucci and Matzinger,
2001; McFadden and Basketter, 2000). In fact, as most allergens have irritant
et al., 2002).
