Evaluation of IL-9, IL-10, IL-13 and IL-15 as biomarkers of dermal exposure to respiratory sensitizers.
Manetz-TS; Pettit-D; Meade-BJ
Toxicologist 2001 Mar; 60(1):8
Differential modulation of mRNA and protein levels for interleukin-4 (IL-4), IL10 and interferon gamma by respiratory and T cell mediated sensitizers has been demonstrated. The following investigation examined the mRNA expression patterns of multiple cytokines associated with respiratory sensitization for modulation using a Multiprobe Ribonuclease Protection Assay. Female BALB/c mice were dermally exposed on the shaven dorsal lumbar area with either vehicle or test article on Day 0 and Day 5 followed 5 days later by exposure on the ear pinna for 3 consecutive days to chemicals known to primarily induce irritation (Sodium 1auryl Sulfate), respiratory sensitization (Toluene Diisocyanate), or T cell-mediated hypersensitivity (Dinitrofluorobenzene) responses. Draining lymph nodes were excised and mRNA isolated immediately or following 24 or 48 hrs in culture with Concanavalin A (Con A). Differential expression of cytokine mRNA was most notable in animals receiving test article only on the ears (no previous induction) following 24 hr incubation with Con A. The response for IL-4, IL-10, and IFN-y was consistent with previous studies by others. In addition, IL-9, IL-13 and IL-15 were significantly elevated only following TDI exposure. The most robust modulation (>200 fold increase over control) was observed for IL-13 which shares many biological activities with IL-4 and has been shown to be required for the induction of airway hyper-responsiveness in mice. Further investigations of these cytokines may provide additional insight into the mechanisms of chemically induced respiratory sensitization and provide endpoints for screening methods aimed at identifying chemicals with the capacity to elicit pulmonary sensitization.
Biomarkers; Sensitization; Hypersensitivity; Exposure-levels; Laboratory-animals; Animals; Animal-studies; Biological-factors; Respiratory-hypersensitivity; Respiratory-system-disorders; Pulmonary-system-disorders
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California