Toxicology of Industrial Compounds

Table 10.2 The cytokine products of murine Th 1 and Th 2 cells
From: Mosmann and Coffman (1989).
I.KIMBER 141
1994). The implication is that certain chemicals favour the development of
Th 2 cells which will then synthesize and secrete IL-4 and thereby encourage
IgE antibody responses and mast cell sensitization. The converse is that
other classes of chemical allergen preferentially stimulate Th1 cells and IFNproduction.
Such conditions will be nonpermissive for IgE antibody
production and cell-mediated immune responses, including contact
sensitization, will be favoured instead. A selective stimulation by different
classes of chemical sensitizers of divergent Th responses may provide an
explanation at the cellular level for the observation that chemicals vary
with respect to the nature of allergic reactions that they will elicit
preferentially in man. The stimulation by chemical allergens of
differentiated Th cell responses may have implications for allergic disease
other than the regulation of IgE antibody. It is known for instance that
IL-3, IL-4 and IL-10, all of which are products of murine Th 2 cells
(Table 10.2), act as mast cell growth factors or cofactors (Smith and
Rennick, 1986; Thompson-Snipes et al., 1991). Moreover, IL-5 is a growth
and differentiation factor for eosinophils (Yokota et al., 1987) and serves
to regulate the accumulation of these cells at the site of allergeninduced
hypersensitivity reactions in the respiratory tract (Gulbenkian et al., 1992).
It has been found recently that the cytokines IL-3 and IL-4 also enhance the
secretory activity of mast cells following activation (Coleman et al., 1993).
Antagonistic and inhibitory influences of Th cell products may also affect
the elicitation of allergic reactions. It has been found that IFN- not only
suppresses the secretory function of mast cells (Holliday et al., 1994), but
also antagonizes the antigen-induced infiltration of eosinophils into the
respiratory tract of sensitized mice (Iwamoto et al., 1993). Contact allergic
reactions may in theory be regulated by Th 2 cytokines. It has been shown
that IL-4 and IL-10 act in concert to inhibit Th 1 cell function and to