Age-dependent alterations in the tumoricidal functions of tumor-associatedmacrophages

Age-dependent tumor cytolytic functions of tumor-associated macrophages (TA M) obtained from mice bearing different stages of Dalton's lymphoma (DL), a spontaneous T cell lymphoma, were studied. Mice were separated into three groups on the basis of their reproductive status as indicator of age: young (prereproductive); adult (reproductive) and old (postreproductive). DL was injected (1 x 10(5) cells/mouse) intraperitoneally in mice; days 4, 10 and 16 from the day of injection were referred to as early, mid and late tumor stages, respectively. Normal peritoneal macrophages and macrophages isolat ed from the ascitic fluid of DL-bearing mice (TAM); 1 x 10(5) cells activat ed with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) and assa yed for age-dependent alterations in macrophage tumoricidal functions such as: tumor cell binding, cytotoxicity, production of reactive nitrogen inter mediates (RNI), expression of inducible nitric oxide synthase (iNOS) and on costatin-M (OSM) were observed. TAM from old mice were observed to be inhib ited with respect to tumor cell binding, cytotoxicity and expression of iNO S and OSM, as compared to macrophages of young and adult mice. TAM obtained from early tumor stages showed augmented tumor cytotoxicity as well as enh anced expression of INOS and OSM in all the age groups. This effect was mos t pronounced in the TAM obtained from adult mice and least in the TAM obtai ned from old mice. The reasons for the observed difference are discussed. T hese observations should be helpful in understanding the effect of progress ive tumor growth and age on the functions of TAM and their responsiveness t owards therapeutic manipulations.