Inflammation is a physiologic response to antigenic stimulation that occurs to rid the body of
the infectious stimulus and that is localized to the site in the body where the infectious agent is
found. Clinical signs of inflammation include pain, heat, redness, and swelling, which result from a
number of physiologic changes that take place during the inflammatory response:  altered patterns
of blood flow (redness, heat); fluid leakage out of small blood vessels (swelling, pain); and influx of
phagocytic or other immune cells (swelling)

Under normal circumstances, inflammatory response to infection or tissue injury is rapid—initiated
within minutes of the pathogenic stimulus, and leads to efficient removal of the stimulating agent

Two phases of inflammation have been identified.  The initial phase is the inflammatory phase,
which involves (a) destruction or sequestration of the invading pathogenic agent and (b) removal of
necrotic cells and debris.  The subsequent phase is the reparative phase which incorporates
aspects of wound healing.  If repair is successful, the affected tissue will be returned to its original
state and function.  In cases of extensive or prolonged inflammation, the affected tissue is replaced
by fibrotic scar tissue.

Measurement

Prominent measures of inflammation include quantitative assessment of the pro-inflammatory
cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor- (TNF-), the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10)
(see http://pmbcii.psy.cmu.edu/core_e/cytokines.html), and total or specific white blood cell
counts (see http://pmbcii.psy.cmu.edu/core_e/common_immune_assays.html).  Other measures
of inflammation include detection and quantification of APPs, cellular adhesion molecules,
chemokines, and markers of allergic inflammatory response (e.g., protein products of inflammatory
cells).  Table 1 below lists a number of commonly measured biomarkers of inflammation, their
availability in biological samples, and frequently used assays.
Table 1 provides neither an exhaustive catalogue of all available measures of inflammation, nor
recommendations for which measures to employ.  Rather, it provides an overview of the types of
measures commonly used in research.

Table 1. Biomarkers of inflammation

ELISA = enzyme-linked immunosorbant assay; FIA = Fluorescence Immunoassay;
hs-CRP ELISA = high sensitivity CRP enzyme-linked immunosorbant assay;
IN = immunonephelometry; IL = immunoluminometry; IT = immunoturbidimetry

Physiological Mechanisms

Infection or injury to tissue stimulates recruitment of mast cells to the affected site.  Mast cells
secrete pro-inflammatory factors (e.g., histamine) which act on local blood vessels to increase
delivery of blood, plasma and additional inflammatory cells to the site.  Included among the
inflammatory cells are neutrophils and macrophages which kill and ingest invading pathogens.
Prolonged inflammation stimulates macrophage secretion of pro-inflammatory cytokines.
Cytokines promote further inflammatory activity by increasing the number of leukocyte adhesion
molecules on endothelial cells proximal to the affected site.  This enhanced expression of
adhesion molecules results in local accumulation of cells of the immune system such as
CD4+ T and B lymphocytes, as well as additional monocyte-derived macrophages.  In the
case of chronic infection, pro-inflammatory cytokines released from lymphocytes
(e.g., IL-1, IL-6, TNF-) can enter the systemic circulation and ultimately elicit a hepatic APR.

In the case of allergic inflammation, initial activation of resident mast cells is stimulated by a
mechanism involving immunoglobulin E (IgE) rather than pathogenic tissue insult.  Activated
mast cells respond to the allergic stimulus by releasing factors (e.g., TNF-, GM-CSF) that
recruit and activate eosinophils.  Eosinophils, in turn, produce factors that can promote survival
and further activation of mast cells, thus contributing to a forward-feeding process of prolonging
and intensifying allergic response.

Recommended Reading
Adamko, D., Lacy, P., & Moqbel, R. (2004).  Eosinophil function in allergic inflammation:
From bone marrow to tissue response. Current Allergy and Asthma Reports, 4, 149-158.
Rabin, B.S. (1999). Overview of the Function of the Immune System. In B.S. Rabin,
Stress, immune function, and health: The connection.  New York, NY: Wiley-Liss.
Roberts, W.L., Moulton, L., Law, T.C., Farrow, G., Cooper-Anderson, M., Savory, J., & Rifai,
N. (2001). Evaluation of nine automated high-sensitivity C-reactive protein methods:
Implications for clinical and epidemiological applications. Part 2. Clinical Chemistry, 47(3),
418-425.
Silkoff, P.E. (2000). Noninvasive measurement of airway inflammation using exhaled nitric
oxide and induced sputum. Current status and future use. Clinics in Chest Medicine,
21(2), 345-360. 
Vig, R.S., Forsythe, P., & Vliagoftis, H. (2006). The role of stress in asthma. Insight from
studies on the effect of acute and chronic stressors in models of airway inflammation.
Annals of the New York Academy of Sciences, 1088, 65-77. 

Core-E MainBiological Measures Used