EFFECT OF AGING ON THE TUMORICIDAL FUNCTIONS OF MURINE PERITONEAL-MACROPHAGES

The present investigation was carried out to study the effect of aging on the activation of murine peritoneal macrophages by lipopolysacchar ide (LPS) plus interferon-gamma (IFN-gamma) to tumoricidal state. Age- dependent alteration in macrophage-mediated tumor cell binding, cytoto xicity, cytostasis and production of the tumoricidal effector molecule s oncostatin M, tumor necrosis factor and nitric oxide (NO) was studie d. Macrophages (1.5 x 10(5)) obtained from mice of different age group s were separated on the basis of the reproductive status of the mice i nto prereproductive (young), reproductive (adult) and postreproductive (old) for studying their activation. Macrophages obtained from the ol d mice were found to be least responsive to the activation signal of L PS+IFN-gamma for macrophage-mediated tumoricidal activity and producti on of effector molecules. The macrophages of the old mice did not expr ess inducible nitric oxide synthase, an enzyme responsible for the pro duction of NO by activated macrophages. Macrophages of the adult and y oung groups showed better response; however, optimal response was obse rved in the macrophages of adult mice. The reasons for the observed di fference in the response of macrophages are discussed.