Biomedical Engineering Reference
In-Depth Information
site in intron 2 containing two to six repeats of an 86 base pair sequence
(136). There is evidence that allele 2 of the IL1RN gene (IL1RN
2) is asso-
ciated with increased susceptibility or more severe outcome in chronic
inflammatory diseases such as ulcerative colitis, systemic lupus erythemato-
sus, and alopecia areata (137-139). The IL1B C-511T has been associated
with inflammatory bowel disease (140), as well as with plasma levels of
IL1B and IL1RN (141).
In a recent study, individual IL-1 genotypes were not associated with
rate of decline of lung function in smokers. However, there was a significant
influence of combinations of IL1RN
=
IL1B alleles in these individuals (142).
The association of these haplotypes with the decline of lung function may
represent an interaction between the genes. A smaller study in a Japanese
population found no association with individual IL1B and IL1RN geno-
types and COPD (129).
IL-13 and IL-13 Receptor:
Targeted expression of IL-13 in the adult
murine lung has been shown to cause emphysema, elevated mucus produc-
tion, and inflammation reminiscent of human COPD (143). Interleukin-13
operates through the IL-13 receptor (IL13R), which is composed of one
IL-4 receptor
a
(IL4RA) subunit and either a low-affinity IL13RA1 or a
high-affinity IL13RA2 subunit (144). IL13, IL13RA1, and IL4RA are
polymorphic. A study found an association of a promoter polymorphism
(C-1055T) of IL-13 with COPD in a Caucasian population (145). Another
recent study suggested the IL4RA 551RR genotype was associated with
rapid decline of lung function (OR
ΒΌ
2.24) (146).
Interleukin-10:
Interleukin-10 is an important immunoregulatory
cytokine produced by many cell types. Its main biological function is to inhi-
bit the production of a variety of proinflammatory mediators (147). In addi-
tion, IL-10 may regulate the balance between proteases and antiproteases
produced by airway macrophages (148,149). Therefore, IL-10 may be
involved in chronic airway inflammation observed in asthma and COPD.
Studies have found that airway IL-10 level was significantly lower in asthma
and COPD patients and in healthy smokers compared with that in healthy
nonsmokers (150). Polymorphisms in the IL-10 promoter could affect the
level of IL-10 expression (151,152). A recent study found that homozygosity
for the 3368G allele was associated with rapid decline of lung function in
woman smokers (153).
5.
Mucocilliary Clearance
The rate at which particulate matter is cleared from the lungs is highly vari-
able between individuals (154). The tracheobronchial clearance rate of
6-7
m
m particles was studied in nine pairs of MZ and nine pairs of DZ twins
(155). The intrapair correlation in clearance rates was significantly higher in
the MZ twins vs. the DZ twins, suggesting that genetic factors may affect an
