Peripheral blood mononuclear cells (PBMC) of frail elderly nursing home residents had significantly higher PHA-induced interleukin-10 (IL-10) production compared to PBMC's from young control subjects. No correlation was observed between IL-10 production and interleukin-12 (IL-12) p40 production, proliferative response or with the proportion of CD28-negative T cells. To better characterize the host response to a ubiquitous pathogen, the dose response and time-dependent (kinetic) production of IL-10 and IL-12 p40 of PBMC stimulated with Staphylococcus aureus Cowan (SAC) was studied. IL-10 production continued to increase at 48 h, while IL-12 p40 levels declined or remained stable, in both young and elderly subjects. In analyzing how excessive IL-10 production might influence antigen presenting cell functions, IL-12 was markedly inhibited by recombinant IL-10 (rIL-10), while anti-IL-10 enhances IL-12 p40 production in cultures from young controls; but the PBMC cultured from an elderly cohort were not able to generate similar absolute levels of IL-12 p40 even in the presence of anti-IL-10. These preliminary data suggest that there may be both over production of IL-10 in some individuals, as well an an impaired ability to upregulate a T Helper 1 (type 1) reaction. These age-related changes could even be more dramatic at the tissue level and contribute to the impaired delayed type hypersensitivity (DTH) and failed host defense to infection, such as to primary and reactivation tuberculosis.