Immunotoxicity Testing

Dori R. Germolec, Kelly A. Shipkowski, Rachel P. Frawley, Ellen Evans, Germolec, Dori R., Shipkowski, Kelly A., Frawley, Rachel P., Evans, Ellen

Inflammation is a complex and necessary component of the response to biological, chemical, or physical stimuli, and the cellular and molecular events that initiate and regulate the interactions between the various players in the inflammatory process remain a source of ongoing investigation. In the acute phase of the inflammatory response, cells of the immune system migrate to the site of injury in a carefully orchestrated sequence of events that is facilitated by soluble mediators such as cytokines, chemokines, and acute-phase proteins. Depending on the degree of injury, this acute phase may be sufficient to resolve the damage and initiate healing processes. Persistent inflammation, either as a result of prolonged exposure to stimulation or an inappropriate reaction against self-molecules, can lead to the chronic phase, in which tissue damage and fibrosis can occur. Chronic inflammation has been reported to contribute to numerous diseases, including arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, and cancer, and to conditions of aging. Hematology and clinical chemistry data from standard toxicology studies can provide an initial indication of the presence and sometimes the location of inflammation. These data may suggest more specific immune function assays that are necessary to determine the presence and/or mechanism(s) of immunomodulation. Although changes in hematology dynamics, acute-phase proteins, complement factors, and cytokines are common to virtually all inflammatory conditions, and can be measured by a variety of techniques, individual biomarkers have yet to be strongly associated with specific pathologic events. Thus, although sensitive indicators of inflammation, these factors generally lack the specificity to identify the offending cause. The profile seen in a given inflammatory condition is dependent on the severity, chronicity, and mechanisms involved in the inflammatory process, as well as the species and the capacity of the individual's immune system to respond and adapt.