Viral and bacterial infections have been indicated as a risk factor for Coronary Heart Disease (CHD). NK cells, as a first line of defense against those infections, therefore may play a role in CHD development. In the particular case of the elderly adults, NK cells may be the primary pathway of antiviral defense [14 ] . A recent study has now demonstrated a specific association between Coronary Heart Disease and the general NK cell impairment, showing lower NK cytotoxic activity in CHD patients as compared to age-matched healthy controls [15 ] .
The trial findings showed CHD patients to have a significantly lower total count and proportion of NK cells and of the more cytotoxic CD56dim cells subpopulation. The percentage of CD56bright regulatory NK cells was also lower in the CHD patients, although not at a statistically significant level. As a marker of NK activity, the production of intracellular IFN-γ in CD3-CD56+ NK cells was found to be slightly lower in CHD patients as well.
Obesity/Metabolic Syndrome & Non–Insulin-Dependent Diabetes Mellitus (NIDDM) Obesity as a condition prodromal to CHD, Metabolic Syndrome and NIDDM, is characterized by a generalized pro-inflammatory state. Pathophysiologically, it notable for: reduced levels of ghrelin, an appetite-stimulating peptide hormone with anti-inflammatory properties, and increased levels of leptin (an appetite-suppressing peptide hormone). This leads to leptin resistance, a heightened release of pro-inflammatory cytokines (including IL-6 and TNF-α) and of the inflammatory marker C-reactive protein (CRP).
The shift in the balance of ghrelin and leptin also disrupts their delicate positive and negative feedback control over Neuropeptide Y (NPY) activity. NPY, ghrelin and leptin all play a major role in the regulation of humoral and cellular immune activity, and their collective imbalance promotes an inhibition of apoptotic behavior in lymphocytes, suppression of NK cell activity inhibition, and oxidative stress in the form of superoxide anion production in macrophages [16-18 ].
Cancer Presently, there is a clear and urgent concern in the area of advanced adult oncology, given that the adult population is rapidly growing and advancing in age, concurrent with its meteoric rise in the frequency of obesity. The global incidence is thus trending strongly upward in a class of diseases for which there is no reliably effective medical remedy. As the number of cancer patients grows ever more rapidly, there is clearly a demand for the development of deeper insights into the basic mechanisms of oncogenesis in normal healthy adults, to yield specific new clinical strategies for the prevention, detection and cure of cancer in the aging adult population.
At the leading edge of clinical and research oncology is the issue of new and growing risk factors for Cancer which affect the general population. Given the aforementioned pro-inflammatory nature of obesity, it naturally follows that the current worldwide trend toward increasing obesity and diminished physical exertion also directly impacts upon cancer prevalence. Based upon studies performed by the International Agency for Research on Cancer, it is estimated that 25% of cancer cases worldwide may be directly attributed to obesity and sedentary lifestyle.
Despite the profound impact of obesity, the best of current scientific evidence indicates unequivocally that the single greatest risk factor for the development of cancer is that of advancing age. Specifically, the incidence of cancer increases in those adults of advanced age whom demonstrate age-dependent progressive immunosenescence.
Intervention
Biopharmaceutical Immunotherapy Immunotherapy, or biologic therapy, employs substances called biological response modifiers (BRMs). Biologic therapies produced in biotechnology and biopharmaceutical laboratories—including monoclonal antibodies, interferons, interleukins, and several types of colony-stimulating factors—are used in the treatment of cancer, rheumatoid arthritis, hepatitis C and other diseases.
Side-effects caused by these types of biopharmaceutical therapies vary with the type of treatment, and often cause chills and fever, loss of appetite, nausea, vomiting, and diarrhea. Depending on the severity of these problems, patients may find their health further compromised, frequently requiring hospitalization during, or as a result of their treatment.
One class of BRMs is referred to as “Immunomodulators”. Pharmaceutical and biopharmaceutical immunomodulators typically function to either upregulate (i.e., immunostimulators) or downregulate (i.e., immunosuppressants) the human immune response. General examples of immunostimulators would be isoprinosine nucleoside, a cytokine like Granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as vaccines and vaccine adjuvants.
Some examples of
immunosuppressants would include corticosteroids, certain monoclonal antibodies, and drugs like cyclosporine, azathioprine,
6-mercaptopurine. Because immunosuppressants tend to act non-selectively, they render the immune
system less able to defend against infections and malignant metastasis. Additional serious side-effects include liver and kidney damage,
peptic ulceration, hypertension, hyperglycemia, and dyslipidemia. |
