Physiological Responses to Cisplatin Using a Mouse Hypersensitivity Model
The physiological mechanisms underlying the development of hypersensitivity to cisplatin (CDDP) are not well-understood. It has been suggested that these reactions are likely the result of the development of type I hypersensitivity, but other explanations are plausible and the potential for CDDP to induce type I hypersensitivity responses has not been directly evaluated in an animal model. To investigate CDDP hypersensitivity, mice were topically sensitized through application of CDDP before being challenged by oropharyngeal aspiration with CDDP. Before and immediately after OPA challenge, pulmonary responses were assessed using whole body plethysmography (WBP). CDDP did not induce an immediate response or alter the respiratory rate in sensitized mice. Two days later, baseline Penh values were significantly elevated (p<0.05) in mice challenged with CDDP. When exposed to methacholine (Mch) aerosol, Penh values were significantly elevated (p<0.05) in sensitized mice and the respiratory rate was reduced (p<0.05). Lymph node cell counts and IgE levels indicate that the mice were sensitized to CDDP. The cellular composition of bronchoalveolar lavage fluid (BALF) harvested from sensitized mice shifted from being dominated by macrophages to neutrophils following CDDP challenge. BALF from sensitized mice also contained ~7% eosinophils compared to less than 0.5% in non-sensitized mice (p<0.05). These data provide previously unknown insights into the mechanisms of CDDP hypersensitivity.