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 0.2g lanolin, the leucocyte count and IL-b content in the abdominal cavity increases to up to 3.6 x 10(6) cells and 1.4 ng, respectively. INF-gamma content in the cavity after application of a mixture of 10 KE OK-432 and 0.2 g lanolin also increases, although not after application of the 5 KE OH-432 mixture of 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 of 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 of subcutaneous injection increases 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.
Matsuoka
H
H
Clinical Research Institute, National Kyushu Cancer Center, Japan.
Yano
K
K
Wasasugi
H
H
Seo
Y
Y
Saito
T
T
Tomoda
H
H
D000009:Abdominal Muscles; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007109:Immunity / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009824:Ointments; D010844:Picibanil / Q000008:administration & dosage* / Q000009:adverse effects; D011208:Powders; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007376:Interleukin-2; D015850:Interleukin-6; D009824:Ointments; D011208:Powders; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D007371:Interferon-gamma