Restoration of immune responses of aging hamsters by treatment with isoprinosine.

Immune competence declines with advanced age in hamsters, as in other laboratory mammals and in humans. We found significant alterations in the functional parameters of different populations of immunocytes (natural killer cells, T cells, monocytes, and suppressor cells) in aging hamsters, beginning at approximately 14 mo of age. Natural killer cytotoxicity, phytohemagglutinin-induced lymphocyte stimulation, and monocyte chemotaxis were decreased in aging Lak:LvG(Syr) outbred hamsters. When old hamsters were given a single injection (5 mg/kg body wt) of isoprinosine, a chemical immune potentiator, these three immune parameters increased almost to the levels found in young adult hamsters but returned to pretreatment levels after 7 d. Suppressor cell activity for the lymphocyte response to phytohemagglutinin, which increased with age, was decreased after treatment. In old hamsters treated with weekly injections of isoprinosine, these four immunological parameters remained at or near the levels found in young adults.

An in vitro study on the effects of isoprinosine on immune responses in cancer patients.

The in vitro effects of ISO on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). For in vitro studies, an optimum concentration of ISO (100 micrograms/ml per 10(6) cells) was used to treat peripheral blood mononuclear cells. In the presence of ISO, all three parameters were restored to normal or near normal levels in those that were depressed. Under these preincubation conditions in vitro treatment of mononuclear cells from the peripheral blood of normal individuals with ISO had no effect on their activities in the three assays. Similar effects on these three immune parameters were observed when 24 h supernatants obtained from patients' mononuclear cells pretreated with ISO were employed in these assays.

Osteosarcoma patients: isolation of serum antibodies by affinity chromatography.

Antibodies specific for membrane-associated antigens of human osteosarcoma cells were isolated from sera of 12 patients with osteosarcoma (OS). Affinity columns were prepared by coupling purified membrane antigens from cultured human OS cell lines (TE-85 or LM) to CBrN-activated Sepharose 4B. The antigens were prepared by discontinuous sucrose gradient ultracentrifugation, papain digestion, and DEAE column chromatography. Diluted serum was passed over the affinity columns, and the adsorbed proteins were eluted with 2.5 M MgCl2 (pH 6.5). Immunodiffusion, indirect immunofluorescence, and complement fixation were used to assay antibody activity in the eluate. Specific anti-OS activity was found in the immunoglobulin (Ig) fraction isolated from the sera of the 12 OS patients, as confirmed by blocking experiments. No anti-OS antibody activity was found in sera from healthy individuals or patients with breast carcinoma, clear cell liposarcoma, or leukemia in this study. The anti-OS activity of the isolated Ig from OS patients was abolished after absorption with cultured human OS cells from lines LM, TE-85, or G292 but not after absorption with cells from lines WI-38 (embryonic lung), TE-32 (rhabdomyosarcoma), CAMA-1 or SW527 (breast carcinoma), or M-14 (melanoma). Absorption with rabbit antihuman IgG but not with rabbit antihuman IgM immunobeads completely eliminated the antibody activity.