Activation of tumor-associated macrophages by thymosin alpha 1

It was shown earlier that the progressive growth of a transplantable T-cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), in a murine host is associated with an inhibition of macrophages (TAM) along with an involution of thymus. However, it remained unclear if a decline in the level of thymic peptides in DL-bearing host, due to thymic regression, has any implications in the inhibited responses of TAM. Therefore, the present investigation was under taken to study whether the TAM of DL-bearing host can be activated to tumoricidal state by peptides of thymic origin. It was observed that intraperitoneal administration of thymosin alpha 1 to DL-bearing mice resulted in activation of TAM. Such TAM were found to produce enhanced amount of interleukin-1 (IL-1), tumor necrosis factor (TNF), reactive oxygen intermediates (ROI), nitric oxide (NO) and showed an increased abilities of pinocytosis, phagocytosis, antigen presentation and tumor cytotoxicity. The TAM were found to be directly responsive to thymosin alpha1 as in vitro treatment with thymosin alpha 1 could activate TAM to tumoricidal state. Treatment of TAM with thymosin alpha 1 also enhanced their LPS responsiveness for an augmented state of activation. The findings of this study demonstrate for the first time that the TAM of a T cell lymphoma can be activated to tumoricidal state by thymosin alpha 1.