Involution of the thymus in tumor-bearing mice and its restoration by PSK. II. Mechanism of the involution and its restoration.

In C3H/He mice, the weight and cell number of the thymus were reduced and the size distribution (scatter profile measured by flow cytometer) of the thymus cells was changed 1 week after subcutaneous inoculation of X5563 plasmacytoma. This involution and change were prevented by intraperitoneal or oral administration of PSK. We examined the mechanism of this involution and change in thymus and the effect of PSK on them. In X5563-bearing C3H/He mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only per organ but also per 1 mg of thymus tissue. Such reduction was inhibited by PSK. The substance (IS substance) which possessed a suppressive activity against mitogen induced lymphocyte proliferation, was partially purified from the ascites of X5563-bearing mice by the combination of ammonium sulfate precipitation and Sephacryl S-200 chromatography. IS substance was demonstrated to suppress the antibody response and delayed type foot-pad response against sheep red blood cells in mice. The reduction of weight and cell number and the change of scatter profile in thymus were caused by injection of this substance even in tumor-free mice. The restorative effects of PSK were observed also in IS substance injected mice. These results suggested that the various changes in the thymus observed in tumor-bearing mice might be attributable to the suppression of cell proliferation in the thymus, that such suppression was caused at least partly by an immunosuppressive substance which possessed inhibitory activity against lymphocyte proliferation, and that PSK had an antagonistic activity against such a substance so as to restore the function of the thymus in tumor-bearing hosts.