THE ROLE OF CHRONC INFLAMMATION IN NON COMMUNICABLE

DISEASES

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Inflammation is the local physiological response to tissue injury. It is not, in itself, a
disease, but is usually a manifestation of disease. Inflammation may have beneficial
effects, such as the destruction of invading micro-organisms and the wailing-off of an
abscess cavity, thus preventing spread of infection. Equally, it may produce diseases;
for example, an abscess in the brain would act as a space-occupying lesion
compressing vital surrounding structures, or fibrosis resulting from chronic inflammation
may distort the tissues and permanently alter their function. Inflammation plays an
important role in the pathogenesis of atherosclerosis, thrombosis, clinical cardiovascular
disease diabetes, cancer and various joint diseases.

Chronic Inflammation and Cancer

We will consider the role of inflammation in the pathogenesis of gastric cancer.

Helicobacter pylori induce infiltration of the gastric mucosa by polymorphonuclear cells

and macrophages, as well as T and B lymphocytes. Paradoxically, this robust
immune/inflammatory response cannot clear the infection, and thus leaves the host
prone to complications resulting from chronic inflammation. One adverse consequence
of this inflammatory response may be gastric cancer, as inflammation has been
implicated in the development of intestinal metaplasia and mutations in oncogenes that
precede the development of gastric adenocarcinoma. The gastric inflammatory
response is affected somewhat, by the strain of H. pylori that infects the host. Thus, the
more severe clinical manifestation associated with some strains may be attributed to the
higher grade of inflammation that they induce. Both H. pylori and cytokines induced
during infection can stimulate the recruitment and activation of inflammatory cells
including neutrophils and macrophages. When activated, these cells produce
inflammatory mediators that include reactive oxygen species (ROS). These mediators
impart an oxidative stress on the cells in the immediate vicinity, in this case, the gastric
epithelium. Normally, oxidative stress is neutralized by natural antioxidants such as
vitamin C; however, levels of this antioxidant in the gastric juice are decreased during
infection. The increased levels of oxidants and decreased antioxidants create a stress
that can change many processes in the gastric epithelium. For example, an
accumulation of intracellular ROS regulates the expression of many genes and can
induce DNA damage. Point mutations in the DNA that disrupt the expression and
function of genes that inhibit cell growth (i.e. p53) are believed to contribute to the
pathogenesis of gastric cancer. Several studies suggest that epithelial cell turnover is
affected by the inflammatory response to H. pylori. This notion is supported by studies
describing an increase in both epithelial cell proliferation, as well as cell death by
apoptosis, in response to infection. Apoptosis is a regulated process of cell death that is
triggered by H. pylori as well as various inflammatory mediators, including tumour
necrosis factor and interferon-gamma. Activated T-cells also kill gastric epithelial cells
directly. Moreover, the host response increases the expression of receptors for H. pylori
and thus increases bacterial binding and the induction of apoptosis by the bacteria.
There are several other immune/inflammatory responses that contribute to epithelial cell
damage mucosa and the pathogenesis of gastric cancer. For example, gastric B cells
produce autoreactive antibodies that bind to gastric epithelial cells. As a consequence
of this antigen-antibody complex formation, complement becomes activated suggesting
that some of the inflammation and epithelial cell damage is attributable to immune-
complex formation. Epithelial cell death can then stimulate the proliferative response of
epithelial cell precursors. In summary, the proposed model may explain how the gastric
inflammatory response contributes to the pathogenesis of cancer. This model raises the
possibility that it could be preferable to identify the patients at highest risk of developing
gastric cancer and then apply an intervention that eliminates the infection and
inflammatory response. Alternatively, clinical interventions should at least attenuate the
oxidative stress that is directly attributed to inflammation.

Cardiovascular disease
Cardiovascular disease (CVD) is now an emerging epidemic in developing countries
and by year 2010, CVD will be the leading cause of death in the developing countries.
Life style changes brought about by industrialization and urbanization in developing
countries is a factor. Traditional risk factors like tobacco, alcohol, hypertension and
physical inactivity should be avoided. However, prevention of infection, immunization
and vaccination against common infections may also be a very important part of
preventive cardiology in developing countries.

Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an

ongoing inflammatory response. Recent advances in basic science have established a
fundamental role for inflammation in mediating all stages of this disease from initiation
through progression and, ultimately, the thrombotic complications of atherosclerosis.
These new findings provide important links between risk factors and the mechanisms of
atherogenesis. Clinical studies have shown that this emerging biology of inflammation in
atherosclerosis applies directly to human patients. Elevation in markers of inflammation
predicts outcomes of patients with acute coronary syndromes, independently of
myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels
of the inflammatory marker C-reactive protein (CRP), prospectively defines risk of
atherosclerotic complications, thus adding to prognostic information provided by
traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit
inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does
not appear to correlate with reduction in low-density lipoprotein levels. These new
insights into inflammation in atherosclerosis not only increase our understanding of this
disease, but also have practical clinical applications in risk stratification and targeting of
therapy for this scourge of growing worldwide importance

A prospective, nested case-control study was done in the Cardiovascular Health Study
(CHS; 5201 healthy elderly men and women). Case subjects and control subjects
(n=146) were matched on the basis of sex and the presence or absence of significant
subclinical cardiovascular disease (CVD) at baseline (average follow-up, 2.4 years). In
women but not men, the mean CRP level was higher for case subjects than for control
subjects. In general, CRP was higher in those with subclinical disease. Most of the
association of CRP with female case subjects versus control subjects was in the
subgroup with subclinical disease. Case-control differences were greatest when the time
between baseline and the CVD event was shortest. The strongest associations were
with myocardial infarction, and there was an overall odds ratio for incident myocardial
infarction for men and women with subclinical disease. In conclusion, CRP was
associated with incident events in the elderly, especially in those with subclinical
disease at baseline.

Diabetes mellitus- an inflammatory disease

Inflammation is defined as a cascade of phenomena induced in response to different

pathological stimuli. This physiological occurrence that allows the restoration of
homeostasis may also cause different diseases in various pathological conditions.
Inflammatory process seems to play an important role in the development of diabetes
and its late complications. Both genetic and environmental factors, such as diet,
physical inactivity, smoking and stress are responsible for the activation and intensity of
chronic inflammation. Epidemiological, clinical and experimental studies have indicated
an association of low-grade inflammation with type 2 diabetes. Moreover, the role of
inflammation in pathogenesis of type 2 diabetes and vascular complications was
confirmed by intervention studies. It has been shown that loss of weight, increase in
physical activity, treatment with converting enzyme inhibitors, statins, high doses of
aspirin and glitazones reduce the incidence of type 2 diabetes and its vascular
complications partially via anti-inflammatory mechanism. The hypothesis that type 2
diabetes is an inflammatory disease opens new clinical perspectives for diagnosis and
treatment, but still needs to be more explored.
References

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