Theory and practice of cytokine assessment in immunotoxicology.

The tools and concepts of immunotoxicology are increasingly being used in novel ways, such as using toxic reagents to understand immune system function. One of the most potentially useful of these new tools is the assessment of cytokines, the molecules responsible for regulating a variety of processes including immunity, inflammation, apoptosis, and hematopoiesis. Cytokine production or bioactivity may be affected by a variety of toxic mechanisms including direct toxicity to cytokine-producing cells, inhibition of cytokine production, inhibition of cytokine release, induction of immunosuppressive factors, alterations in cellular homeostasis, alterations in cellular activational or transcriptional mechanisms, and miscellaneous or undefined mechanisms. Moreover, alterations in the profile of cytokine production may provide important information regarding the nature of an immunotoxic insult (i.e., TH1 vs TH2 response). Proper evaluation of the role of cytokine modulation in immunotoxicology requires attention to myriad details. Some of the details discussed in this review include the source of the sample to be tested (circulating, local, or ex vivo isolated cells); the potential effects of collection, processing, and storage on the results of the assays; potential variables associated with the source material (matrix effects, relevance, inhibitory substances); and factors influencing the choice of assay used (bioassay, immunoassay, molecular biology technique, flow cytometry, hybrid assays). Other often-overlooked issues are discussed, including species considerations and quality control issues such as the use of reference standards and the expression of results. Copyright 1999 Academic Press.