Murine Model for Contact Sensitization

Abstract

A method combining murine ear swelling and lymph node cell proliferation was evaluated as a quantitative measurement of delayed-contact sensitization. The method involves one and/or four occluded, abdominal induction applications; use of pertussis toxin as an adjuvant; topical challenge to the ear; baseline and postchallenge ear measurements; and measurement of 125I incorporation in axillary lymph nodes after injection of 5-[125I]iodo-2'-deoxyuridine ([125I]UdR). The inclusion of vehicle-induced/test chemical-challenged control groups permits objective recognition of positive responses by statistical analysis. This model—intended for use in screening for the sensitization potential of topical therapeutics—was evaluated with the known sensitizers tetracaine, naloxone, and oxazolone and with the irritant sodium dodecyl sulfate. Axillary lymph node cell proliferation measured by 125I incorporation was a more sensitive measurement of contact sensitization than ear swelling. It was essential to perform both one and four inductions because tetracaine gave the greatest lymph node response after one induction, whereas naloxone produced a sensitization response only after four inductions. Ear swelling response to tetracaine increased after four inductions; however, ear swelling response was not observed after either one or four inductions of naloxone. After one or four inductions of the strong sensitizer, oxazolone, lymph node and ear swelling responses were observed. As expected, no significant ear swelling or lymph node response to sodium dodecyl sulfate was observed after one or four inductions. This method allows quantitative evaluation of contact sensitization by two separate measurements, thereby increasing the potential of identifying sensitizers missed by other methods.