In vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of alpha 1-acid glycoprotein, in connection with its high level in tumor-bearing mice.

Suppressed concanavalin A response of spleen cells which appeared on Day 21 in C3H/He mice bearing methylcholanthrene-induced fibrosarcoma was attributed to macrophages. These macrophages were not only immunoglobulin and Thy 1.2 negative and mitomycin C resistant but were also found in the light-specific-gravity (1.077) fraction and were completely removed by carbonyl iron treatment. These suppressor macrophages, however, disappeared 4 days after surgical resection of the tumor, suggesting that the control mechanism originally resides in tumor tissues. Immunosuppressive acidic protein (IAP) levels in the sera of these tumor-bearing mice increased along with the appearance of these suppressor macrophages. Inasmuch as the suppressor macrophages obtained from the spleens of tumor bearers and cultured in vitro produced 4 times more IAP (88 ng/ml) than did resident macrophages, the elevated levels of IAP in the sera of tumor-bearing mice at the late stage might be explained partly by the appearance of suppressor macrophages. On the other hand, an i.v. administration of IAP (5 mg/mouse) into normal mice not only induced the same unresponsiveness of spleen cells to concanavalin A shown by tumor-bearing mice but also induced suppressor macrophages in the spleens of these mice. This fact may indicate that IAP elevation, even though artificial, triggers the induction of suppressor macrophages in the spleen or at least points to a keen correlation between the appearance of suppressor macrophages and increased IAP level in the serum.