Thymosin alpha 1 restores NK-cell activity and prevents tumor progression in mice immunosuppressed by cytostatics or X-rays.
The effect of thymosin against tumor progression was examined in mice immunosuppressed by cytostatics or X-ray irradiation. When pretreated with cytostatic agents, such as 5-fluorouracil (5-FU) or BCNU, or by X-ray, and then inoculated with P388 or L1210 leukemias, mice died rapidly within a few days. In these systems, thymosin alpha 1 given concomitantly with the cytostatic agents or after X-irradiation prevented rapid death and extended survival, although the mice eventually died with leukemia like normal mice inoculated with cells of the same tumor. Rapid death in the 5-FU-treated mice was also prevented by adoptive transfer of spleen cells from the donor mice if these had been treated with 5-FU plus thymosin alpha 1, but not if they had received 5-FU alone. However, the restorative activity of the donor spleen cells was abrogated by treatment with anti-asialo GM1, but not by treatment with anti-Thy 1 or anti-mouse Ig serum, suggesting that the effector cells in the spleen are NK cells. In fact, thymosin alpha 1, when given concomitantly with 5-FU or after X-irradiation, maintained the NK activity of spleen, which was damaged by treatment with 5-FU or X-irradiation alone. The present study indicates that thymosin alpha 1 exerts a preventive activity against progression of leukemias at least in part through an effect on NK cells or their progenitor cells.
D000818:Animals; D002330:Carmustine / Q000627:therapeutic use*; D005472:Fluorouracil / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D007941:Leukemia P388 / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D007942:Leukemia, Experimental / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013951:Thymus Hormones / Q000494:pharmacology*
D013951:Thymus Hormones; D013947:Thymosin; D005472:Fluorouracil; D002330:Carmustine; D000077596:Thymalfasin