Potential advantages in therapeutic index of OK-432 ointment to abdominal skin over systemic applied in a mouse model

A mixture of OK-432 powder and an ointment base, lanolin, was applied to mouse abdominal skin. After application of the mixture of 5 KE OK-432 and 0.2 g lanolin, the leucocyte count and IL-6 content in the abdominal cavity increased to up to 3.6 × 106 cells and 1.4 ng, respectively. INF-γ content in the cavity after application of a mixture of 10 KE OK-432 and 0.2 g lanolin also increased, although not after application of the 5 KE OK-432 mixture or dorsum subcutaneous injection of a saline solution of 5 KE OK-432. These results indicate that an application of OK-432 mixed in lanolin to the mouse abdomen is able to exert an influence on the immunomodulatory effect in the abdominal cavity. The concentrations of IL-6 in serum after applying the ointment mixture, and subcutaneous or intraperitoneal injection of the saline solution of 5 KE OK-432, were <20, 370, and 430 pg/ml, respectively. After application of the ointment mixture of 5 KE OK-432, serum IL-6 did not increase. IL-6 levels in the abdominal cavity after 5 KE OK-432 ointment or subcutaneous injection increased to up to 1.4 and 2.1 ng/cavity. From these results, the immunomodulatory systemic response of OK-432 brought about by applying OK-432 ointment to the abdominal skin is lower than that brought about by injecting OK-432 subcutaneously. Therefore, it is thought that application of OK-432 ointment might be most suitable for potentiating local immune response.