Health Effects of Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 583

TABLE 23.7
Summary of Adjuvant Effects of Diesel Exhaust Particles on In Vivo Allergic
Responses in Humans a

Nasal allergic responses
Increased production of IgE and IgE-secreting cells [76]
Qualitative difference in IgE isoforms [76,276]
Increased production of allergen-induced antigen-speciic IgE [77]
Induction of broad cytokine proile in the absence of antigen [277]
Induction of Th-2-like cytokine proile with coadministration of intranasal allergen and diesel PM [77]
Allergen-speciic isotype switching of B cells to IgE synthesis
Increased production of chemokines [278]

Source: Modiied from Nel, A.E. et al., J. Allergy Clin. Immunol ., 102, 539, 1998, Table III.
a References cited are those cited by Nel et al.

5

KLH
KLH + DEP

*

4

3

2

1

0

Day 0 Day 29 Day 0 Day 29 Day 0 Day 29 Day 0 Day 29

IL-4 IFN-γ

FIGURE 23.15 Concentration of IL-4 following nasal challenge of atopic subjects with keyhole lim-
pet hemocyanin (KHO-antigen to which humans are not exposed) alone and in combination with diesel
exhaust particles (DEP). IL-4 is a Th-2 lymphocyte cytokine and a potent inducer of IgE antibody whose
levels are increased in persons with “hay fever” and asthma. IFN-γ is a Th-lymphocyte cytokine that is
not thought to participate in IgE-mediated immune response. The igure shows a lack of IL-4 response to
KLH in the absence of DEP and a lack of any IFN-γ response above that seen with KLH alone. Day 29 is
one day after the last of three challenge days. (From Diaz-Sanchez, D. et al., J. Allergy Clin. Immunol .,
104, 1183, 1999.)

In contrast to PM enhancement of IgE-mediated immune pathways, a number of studies have
demonstrated that PM can inhibit cell-mediated immune responses that represent important host
defenses against a variety of microbial pathogens. Studies with Listeria monocytogenes , a bacte-
rium whose clearance is dependent on an intact cell-mediated immune system, have demonstrated
that inhalation and intratracheal instillation of diesel particles lead to decreased alveolar macro-
phage clearance of the bacteria and decreased production of cytokines (IL-1β, IL-12, tumor necro-
sis factor-α [TNF-α]), which are essential for the initiation and maintenance of cellular immune
responses and the production of nitric oxide (NO) that is part of the oxidant antibacterial defense
response [100-102]. Responses to endotoxin, a potent stimulator of IL-12 and TNF-α, were also