The role of eosinophils in the cutaneous lesions of chronic proliferative dermatitis mice

The purpose of the present studies was to investigate the role of eosinophils in the skin of chronic proliferative dermatitis mutant (cpdm/cpdm ) mice to help elucidate potential roles of these leukocytes in allergic disease. The cpdm/cpdm mouse was used to evaluate chemokines involved in eosinophil accumulation in the skin, to assess the potential of neutralizing antibodies against chemokines or cytokines as therapy, and to study the role of eosinophils in cpdm/cpdm mice using these treatments. Increased mRNA expression of Ccl1, Ccl2, Ccl11, Ccl17 , and Ccr3 was observed in the skin of cpdm/cpdm mice. The protein concentration of CCL11 was elevated in skin homogenates, but neutralization of CCL11 with polyclonal antibodies did not affect the number of eosinophils in the skin or the severity of the dermatitis. Neutralization of IL5 with monoclonal antibodies for ten days in mutant cpdm/cpdm mice resulted in a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils compared to mutant littermates. Reducing the number of eosinophils with anti-IL5 resulted in an increased distribution and severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of Arsb, Abp1, and Il10 , mediators that inactivate leukotrienes and histamine and quench inflammation. Skin homogenates from mice treated with anti-IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, and Kitl. The increased severity of alopecia, erythema, and increased epidermal thickness that occur with decreased dermal eosinophils suggest that the key to therapy in this mouse model is not the elimination of eosinophils but in the modulation of eosinophil function to promote their anti-inflammatory effects. Future research is needed to evaluate this role of eosinophils in cpdm/cpdm mice and in other diseases. A method to produce eosinophils from bone marrow cultures in vitro was developed to bypass the limitation on research imposed by the low number of circulating eosinophils in mice