(b) the body system in as markers of

(b) Immunological biomarkersAnother commonly used biomarker of chronic stress is circulating levels of IL-6, TNF-?, C-Reactive Protien (CRP), and IGF-1  (26, 38)The secretion of immunological biomarkers could be altered by the chronic exposure to stress.  Interleukin-6, a pro-inflammatory cytokine which works synergistically with Tumour necrotic factor-? and IL-1 can indirectly capture the dysfunction of the HPA axis mediated by glucocorticoid signalling. CRP levels has been used in many studies as one of the inflammatory responses to chronic stress (55).  These biomarkers however are markers of inflammation, and are not used as primary markers of stress. They are rather indicators of how stress can affect the immune system.  Although they were used with other primary markers such as adrenaline and cortisol to test the relationship between stress and cardiovascular and periodontal diseases (33, 45, 48, 60), they could also be found in the body system in as markers of inflammation in the absence of stress. (c) Metabolic biomarkersChanges in metabolism have also been used as secondary and tertiary markers of stress (32, 34, 48). Studies have used biomarkers such as cholesterol levels, Albumin, Waist-Hip ratio and Glycosylated haemoglobin in combination with other biomarkers as markers of stress. They are however majorly confounded by many variables which make them less reliable and valid measure in epidemiological studies. (d) Allostatic Load No single metric can accurately measure chronic stress and this shortcoming is managed by using a compendium of biomarkers released from different bodily system known as Allostatic load, which is generally defined as the “the price the body pays for being forced to adapt to adverse psychological or physical situations, and it represents either the presence of too much stress, or the inefficient operation of the stress hormone response system” (32).Allostasis is an active physiological or biochemical adaptation that helps the body get back to re-establishing homeostasis after exposure to a stressor. While the acute stress response is critical for survival, repeated or chronic exposure to stressors can have deleterious effects on the nervous, endocrine and immune functions. When individuals are repeatedly exposed to chronic stressors biological responses are induced to cope with these stressors, leading to wear and tear on the immune, cardiovascular, metabolic and nervous systems and is primarily marked by elevated adrenaline and cortisol levels in the body, a phenomenon known as allostatic load (32, 34, 48, 60). When measuring allostatic load information about the status of all major physiological regulatory systems should be considered. The cascading relationships were validated initially by the McArthur Successful Aging Study data and this data contained information about the 10 parameters which determine the physiological status of the HPA axis, sympathetic nervous system, metabolic processes and cardiovascular system. The first four primary mediators pertaining to stress response were DHEA, cortisol, adrenaline and noradrenaline. Other mediators were indices of outcomes; metabolic (e.g. insulin, glucose, total cholesterol, high density lipoprotein, cholesterol, triglycerides, visceral fat depositing), cardiovascular (e.g., systolic and diastolic blood pressure), and immune, e.g., Fibrinogen, C-reactive protein (CRP). Most of the biomarkers measured to derive the allostatic load score are biologically interconnected. Although allostatic load reflects cumulative exposures to stress over many years, most allostatic load studies are of cross sectional. Longitudinal measurement of allostatic load can give information about the allostatic profile of an individual at various stages of developing stress related health outcomes. This can shed some insight into the pathways of pathophysiology leading to the development of disease (28, 34, 33)