Effect of intraperitoneal neutrophils induced by OK432 on malignant ascites.
OBJECTIVE
To evaluate the efficacy of a streptococcal preparation, OK432, on malignant ascites in mice.


METHODS
PC-C203U (PC203) is a preparation of another strain of the streptococcal family, with the lowest antineoplastic action. To examine the survival curves of mice after the inoculation of BAMC-1 tumor cells, we gave intraperitoneal OK432, PC203, or saline as a control. Intraperitonal neutrophils were counted by cytospin, and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1alpha were measured by enzyme-linked immunosorbent assay, and 8 h after the administration of OK432, PC203, and saline. Using electron microscopy, we examined the greater omental milky spots, where the in situ proliferation of neutrophils or macrophages takes place.


RESULTS
The OK432 group had the best survival and the control group the worst. The ratio of intraperitoneal neutrophils to BAMC-1 was highest in the OK432 group and lowest in the control group. Quantitative IL-1beta, IL-6 and MIP-1alpha levels were correlated closely with survival. Electron microscopic examination of the milky spots revealed massive proliferation of neutrophils in the OK432 group, but not in the PC203 or control groups.


CONCLUSIONS
OK432 effectively activated intraperitoneal neutrophils and a series of immunological chain reactions through an increase in IL-1beta, IL-6, and MIP-1alpha levels. Milky spots could have important antitumor effects in terms of the spread of neutrophils.
Hosoya
Yoshinori
Y
Department of Surgery, Jichi Medical School, 3311-1 Minamikawachi, Tochigi, 329-0498, Japan.
Kobayashi
Eiji
E
Takizawa
Toshihiro
T
Fujimura
Akio
A
Yasuda
Yoshikazu
Y
Nagai
Hideo
H
Kanazawa
Kyotaro
K
D000818:Animals; D001201:Ascites / Q000473:pathology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000401:mortality*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010844:Picibanil / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity
D016207:Cytokines; D010844:Picibanil