Activation of murine bone-marrow derived macrophages in vitro with Thymosin-alpha-1 to tumoricidal state: a comparative study on normal and tumour-bearing hosts

The present investigation establishes the ability of Thymosin alpha l (T alpha l) to activate murine bone-marrow derived macrophages (BMDMs) in vitro to tumoricidal state with concomitant release of NO, TNFalpha and IL-1. The T alpha l-induced cytotoxicity and the secretion of soluble lytic factors were both dose- and time dependent. BMDMs cultured from the Dalton's Lymphoma bearing mice (DL-BMDMs) exhibited reduced cytolytic activity towards DL-tumour target cells on activation with T alpha l as compared to the BMDMs obtained from normal mice (N-BMDMs). The DL-BMDMs displayed enhanced TNFalpha and IL-1 release as compared to the N-BMDMs when treated with T alpha l. On the other hand, it is observed that the production of NO and the expression of iNOS was higher in the N-BMDMs as compared to the DL-BMDMs on treatment with T alpha l. Although T alpha l could trigger the tumoricidal functions of BMDMs from normal and DL-tumor bearing hosts, the progressive growth of DL-tumour in ascitic form leads to an alteration in the antitumour response of macrophages. These observations further suggest that a disregulation in the production of inflammatory cytokines like TNF-alpha, IL-1 and the inhibition of NO production in response to DL growth may mutually contribute in explaining the tumour-induced immunosuppression as observed in the DL-bearing mice.