Biomedical Engineering Reference
In-Depth Information
E. Peroxisome Proliferator-Activated Receptor Activators
Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-
activated nuclear hormone receptors belonging to the steroid receptor super-
family, and the three recognized subtypes PPAR-
a
,-
g
,and-
d
are widely
expressed. There is evidence that activation of PPAR-
a
and -
d
may have
anti-inflammatory and immunomodulatory effects (81). For example,
PPAR
g
agonists, such as troglitazone, inhibit the release of inflammatory
cytokines from monocytes and induce apoptosis of T lymphocytes, suggest-
ing that they may have anti-inflammatory effects in COPD (82,83).
F. Adhesion Molecule Blockers
Recruitment of neutrophils, monocytes, and cytotoxic T cells into the lungs
and respiratory tract is dependent on adhesion molecules expressed by these
cells and on endothelial cells in the pulmonary and bronchial circulations.
Several adhesion molecules can now be inhibited pharmacologically. For
example, E-selectin on endothelial cells interacts with sialyl-Lewis
x
on neutro-
phils. A mimic of sialyl-Lewis
x
, bimosiamose, blocks selectins and inhibits
granulocyte adhesion, with preferential effects on neutrophils (84). However,
there are concerns about this therapeutic approach for a chronic disease, as an
impaired neutrophilic response may increase the susceptibility to infection.
The expression of Mac-1 (CDllb
=
CD18) is increased on neutrophils of
patients with COPD, suggesting that targeting this adhesion molecule, which
is also expressed on monocytes and macrophages, might be beneficial (85).
G.
Interleukin-10
Interleukin-10 (IL-10) is a cytokine with a wide spectrum of anti-
inflammatory actions. It inhibits the secretion of TNF-
a
and IL-8 from
macrophages and tips the balance in favor of antiproteases by decreasing
the expression of MMP while increasing the expression of endogenous tissue
inhibitors of MMPs (TIMP). Interleukin-10 concentrations are reduced in
induced sputum from patients with COPD, so that this may be a mechanism
for increasing lung inflammation (86). Interleukin-10 is currently in clinical
trials for other chronic inflammatory diseases (inflammatory bowel disease,
rheumatoid arthritis, and psoriasis), including patients with steroid resistance,
but IL-10 may cause hematological side effects (87). Interleukin-10 may have
therapeutic potential in COPD, especially if a selective activator of IL-10 recep-
tors or unique signal transduction pathways can be developed in the future.
H. Resveratrol
Resveratrol is a phenolic component of red wine that has anti-inflammatory
and antioxidant properties. It has a marked inhibitory effect on cytokine
release from alveolar macrophages from COPD patients that show little
