Toxicology of Industrial Compounds

and local degranulation of mast cells may be necessary for acute
symptoms, late asthmatic responses appearing some hours following
exposure are characterized by an infiltration of mononuclear cells and
increased numbers of leucocytes in bronchoalveolar lavage fluid. Chronic
inflammation is an important component of asthma and, in addition to
mononuclear cell accumulation, is characterized by mucus production, the
destruction and sloughing of airway epithelial cells and subepithelial
fibrosis secondary to collagen deposition. Eosinophils, acting together with
infiltrating T lymphocytes, play a pivotal role in chronic bronchial
inflammation (Corrigan and Kay, 1992). It is apparent also that the
generation of eosinophilia in the respiratory tract is influenced markedly by
Th cell products. As described previously, IL-5 effects the accumulation of
eosinophils at the site of hypersensitivity reactions in respiratory tissues,
while IFN- , secondary to an inhibition of CD4 + cell infiltration,
antagonizes this process (Gulbenkian et al., 1992; Iwamoto et al., 1993). It
may prove that the cell-mediated immune processes relevant to the
development of respiratory hypersensitivity and asthma are also a function
of Th cell heterogeneity. Certainly the stimulation of Th 2 cell activation
will have profound effects on all stages of respiratory allergy. The
infiltration of such cells into sites of encounter with inducing allergen, a
process perhaps facilitated by vasodilation resulting from mast cell
degranulation, will provide a local source of cytokines such as IL-4 and
IL-5. Mast cell secretory activity will be potentiated by the former and
eosinophil accumulation triggered by the latter. That Th 2 cells do in fact
accumulate in the area of immediate-type hypersensitivity reactions is
supported by the studies of Kay et al. (1991) who demonstrated that the
cells infiltrating lesional skin at the sites of late phase cutaneous reactions
in atopic patients produce IL-3, IL-4, IL-5 and GM-CSF, but not IFN- .
Practical applications
I.KIMBER 143
In the course of investigations designed to examine the characteristics of
immune responses induced in mice by chemical sensitizers it was found
that only those materials known to cause respiratory hypersensitivity in
man provoked in mice a substantial increase in the serum concentration of
IgE; a phenomenon thought to reflect the selective stimulation of Th 2 celltype
responses by this class of allergen. It was observed also that contact
allergens known or suspected not to cause occupational respiratory
hypersensitivity failed to result in similar changes in serum IgE levels
(Dearman and Kimber, 1991, 1992; Dearman et al., 1992a,d). The
differential ability of chemical respiratory and contact allergens to
stimulate changes in the concentration of serum IgE in mice forms the basis
of a novel approach to the identification of chemicals which have the
potential to cause sensitization of the respiratory tract. This method, the