Inflammation is the body's mechanism to defend itself against invading organisms and to repair any tissue damage as a result of disease or injury.
The inflammatory process begins with foreign body invasion or tissue damage. Host defense mechanisms work to restore and maintain homeostasis. Most of the body defense elements are located in the blood and with the resulting blood vessel dilation that occurs in inflammation, leukocytes, proteins and fluids enter into the inflamed regions. The symptoms of inflammation are characterized by pain, heat, redness, and swelling.
1. Damage Associated with Chronic Inflammation
2. Inflammation's Link with Cancer
3. CRP/HPT: The Most Sensitive Tests for Inflammation
4. WBC is a Poor Index of Inflammation
5. Inflammation's Link with Coagulation
6. Inflammation's Link with Mortality
7. Effective Uses for an Inflammation Test
8. VDI Tests that Measure Inflammation Damage Associated with Chronic Inflammation
Damage Associated with Chronic Inflammation
"Acute Inflammation Defends, Chronic Inflammation Kills"
Acute (short-term) inflammation is a vital life-sustaining function. The complex cascade of events that occurs is needed to initiate a defense against invading bacteria and to repair tissue damage that occurs from trauma, infection, and disease. While acute inflammation is normally tightly controlled and part of the healing process, chronic (long-term) inflammation is associated with a number of diseases - the most serious being cancer.
One of the most important questions in inflammation research is not why inflammation occurs, but why it does not resolve and why is chronic inflammation linked to so many diseases.
Chronic Inflammation Damages Cells
At the cellular level, the activation of the inflammation begins with production of pro-inflammatory cytokines, chemokines, and free radicals (known as the acute-phase response). These inflammatory substances activate certain white blood cell components which rush to the host's defense. When the neutralization and removal of the deleterious agents (i.e., infectious agents, foreign bodies, or toxins) has occurred, anti-inflammatory signaling occurs for white cell apoptosis (cell death) and the return of tissue to a pre-inflammatory state.
However, if toxic agents remain as a result of infection, foreign body, or environmentally derived substances (diet, poisons, chemicals), a low level long-term activation of the inflammatory process can occur. This long-term activation leads to the production of free radicals and other destructive agents. Tissues/organs in the presence of these agents can lead, with sufficient time, to cellular alterations resulting in disease and cancer.
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Inflammation's Link with Cancer
Neoplasia and Inflammation
There has been a long standing and studied relationship between cancer and inflammation. Epidemiological evidence points to a connection between inflammation and a predisposition for the development of cancer, i.e. long-term inflammation leads to the development of dysplasia.
In cancer, there is evidence that inflammation plays an essential role at each stage of the disease (initiation and proliferation), and both tumor and inflammatory cells are able to directly or indirectly either inhibit or stimulate tumor growth. The effectiveness of tumor development has been demonstrated to correlate directly with the degree of the inflammatory reactions, and it seems that there are interactions between the cytokines produced in response to inflammatory reactions and tumor growth and even indications that inflammatory cytokines favor tumor promotion.
Furthermore, with the assistance of inflammation, tumor cells infiltrate neighboring tissues, enter the bloodstream, migrate, and establish remote colonies (i.e., metastases)
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CRP / HPT: The Most Sensitive Tests for Inflammation
CRP (canine) HPT (feline)
The acute-phase response (APR), initiated by inflammation, is a nonspecific phenomenon of the innate immune response characterized by an increase in certain plasma proteins (acute-phase proteins) after tissue damage. APR is characterized by leukocytosis, fever, alterations in the metabolism of many organs as well as changes in the plasma concentrations of various acute-phase proteins (APP). APP have been defined as any protein whose plasma concentrations increases (positive acute-phase proteins; fibrinogen, serum amyloid A, albumin, C-reactive protein, haptoglobin) or decreases (negative acute-phase proteins; albumin, transferrin, insulin growth factor I) by at least 25 percent during an inflammatory disorder. In dogs, C-reactive protein (CRP) is a major APP and in cats, haptoglobin (HPT) is a major APP. The concentration of CRP / HPT correlates to both the severity and duration of the inflammatory stimuli.
Highly Sensitive Marker of Inflammation
Nakamura, et. al., (2007) examined a wide range of diseases in dogs for CRP. CRP, while nonspecific, is very sensitive to diseases of inflammation and tissue damage. Significantly high values are seen in infection and cancer.
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WBC is a Poor Index of Inflammation
WBC vs. CRP
White blood cell count (WBC), often used as an index of inflammation and infection was demonstrated (Nakamoto, 2007, Matijatko, 2006) to be a poor indicator whereas CRP was very sensitive and quickly dropped with successful therapy.
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Inflammation's Link with Coagulation
Inflammation is known to affect coagulation. Initially, inflammation induces a patient into a hypercoagulation state and with increasing severity advances to systemic hypocoagulation. Comparing CRP to the activated clotting time (ACT), it was found that with increasing levels of inflammation, clotting times increased significantly (Cheng, 2009). Knowing the inflammatory state of the dog before surgery serves as a valuable aid in patient management.
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Inflammation's Link with Mortality
CRP and Mortality
Pain is a hallmark of inflammation. However, when a dog is in pain it can be hard to tell. In the wild, animals hide their pain from the pack and from predators; it can mean the difference between life and death. So by the time signs of illness appear, it is often serious.
In a group of "apparently healthy dogs" CRP was measured and found elevated in 23%. Within 6 to 9 months, 19% of this group died compared to 3% with normal levels of inflammation - a 6 fold increase (Selting, 2012).
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Effective Uses for an Inflammation Test
While APPs are non-specific, they are very sensitive to systemic inflammation. Its non-specificity is actually a benefit for a general wellness screen as one test covers many diseases. Low levels then become a "rule-out" for serious disorders and moderate to high levels become a call-to-action for further diagnostic workups.
Rule-Out/ Monitoring Infection
CRP & HPT have been shown to be 100% sensitive to critical infections. In the workup of a suspected infection, APPs can be used as a "rule-out". WBC has been shown to correlate poorly to infection. APPs can be used to monitor post-therapy recovery.
Dogs & cats in an inflammatory state are at higher risk for post-surgery complications due to coagulation complications and the potential for organ failure due to SIRS.
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VDI Tests that Measure Inflammation
VDI offers APP measurement in a variety of formats:
Canine CRP - Visual Rapid Test
In-house, 5 minute qualitative assessment of inflammation on whole blood. More Info>
Reference lab test (24 hr turn-around-time) for the quantitative measurement of CRP. More Info>
Reference lab test (24 hr turn-around-time) for the quantitative measurement of HPT. More Info>
Reference lab test (24 hr turn-around-time) for dogs with suspected or confirmed cancer. More Info>
Health and cancer screen for the apparently healthy dog. More Info>
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