SUMMARYOK-432 (a streptococcal preparation) has been widely used for cancer immunotherapy in Japan. It is the most potent immunomodulator in activating both macrophages and killer T cells and in increasing interleukin 2 production. Two K.E. (Klinische Einheit, clinical unit) of OK-432 were given intraperitoneally to each of 17 female nonobese diabetic (NOD) mice every week from 4-24 wk of age. NOD mice as well as BB rats spontaneously develop type I diabetes. During administration of OK-432, the development of diabetes was inhibited in 17 of 17 mice over the 24-wk observation period, whereas 14 of 17 female NOD mice given physiological saline had developed diabetes by 24 wk of age. At the onset of diabetes, nonfasting blood glucose was 511 ± 8 2 mg/dl. Histologic examination showed that in the OK-432-treated NOD mice, 98% of total islets were intact or mildly infiltrated with mononuclear cells, whereas in saline-treated NOD mice, 79% of total islets exhibited severe insulitis. In OK-432-treated NOD mice, both the number of the mononuclear spleen cells and their natural killer cell activity was significantly increased. DIABETES 1986; 32:496-99. 10^12 Ultrastructural examinations of female NOD mice show infiltration of macrophages and lymphocytes into the islets and reduction of islet size. 13 As reported previously,

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We have recently shown that a streptococcal preparation (OK-432) inhibits insulitis and prevents diabetes in nonobese diabetic (NOD) mice, an animal model of insulin-dependent diabetes mellitus (IDDM). We extended this study to another model of IDDM, namely BB rats. Male and female BB rats were injected weekly with 0.2 mg OK-432 i.p. starting from 5 to 6 wk and continuing through 20 or 30 wk of age. The cumulative incidence of IDDM over 20 wk in the OK-432-treated BB rats (4 of 54, 7.4%) was significantly (P less than .01) lower than that found in the nontreated BB rats (13 of 47, 27.7%). We examined some of these rats as follows. All of the OK-432-treated BB rats tested showed normal glucose levels before and after oral glucose administrations, as did the nontreated and nondiabetic BB rats. Histological examination of pancreatic sections revealed that the OK-432-treated rats retained a greater number of intact islets without infiltration of the mononuclear cells than did the nontreated BB rats. A preliminary in vitro study further demonstrated that the cytotoxic activities of spleen cells against a rat insulinoma cell line, RIN, were suppressed in the OK-432-treated rat. However, the treatment of BB rats with OK-432 showed no suppressive effects in the spleen cell number, the responsiveness of spleen cells to concanavalin A, the populations of OX19+, W3/25+, and OX8+ peripheral blood lymphocytes, or in the titers of cell surface antibody against RIN. These results suggest that a nonimmunosuppressive immunomodulator such as OK-432 may be useful as an agent for immunotherapy of IDDM.

BACKGROUND: Cells in the arterial wall are normally subjected to approximately 10% cyclic stretch due to pulsatile blood flow. In addition, cells in the walls of abdominal aortic aneurysms (AAA) experience hypoxic conditions caused by the accumulation of intraluminal thrombus. Such combined stimulation by hypoxia and stretch can induce abnormal functions in macrophages that infiltrate into the AAA walls; however, the details of these effects are unknown. OBJECTIVE: The aim of this study is to know the influence of a combination of cyclic stretch and hypoxia on the macrophage morphology. METHODS: Morphological changes, such as aspect ratio and orientation, in macrophages exposed to 10% cyclic stretch and 2.2% O 2 hypoxia during 24 h were evaluated with usage of ImageJ software. We also assessed expression of hypoxia-inducible factor-α (HIF-1α), an intracellular signaling factor, in macrophages by western blotting. RESULTS:The results indicate that hypoxia significantly suppresses stretch-induced orientation in the direction of the stretch and elongation of macrophages. We also found that the combination of cyclic stretch and hypoxia significantly increased HIF-1α expression. CONCLUSIONS: These results suggest that hypoxia suppresses morphological responses of macrophages to cyclic stretch by elevating HIF-1α expression.

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