Senchina and Kohut well as molecular systems such as complement and inﬂam- mation. Dendritic cells reside in the lymphoid tissues and serve as storehouses and presenters of antigen, which they present to activate B cells and T cells; thus, DCs are important in initiat- ing adaptive immune responses. The effects of aging on DC responses have not been studied extensively; however, some of the published data suggest that aging tends to be associated with diminished function. One study reported that peripheral blood plasmacytoid dendritic cell numbers declined with age, and that the in vitro IFN-α-producing ability of these cells also decreased with age (Shodell and Siegal 2002). Human monocyte-derived dendritic cells showed no reduction in an- tigen-presenting abilities with age (Lung et al 2000); however, research on mice has suggested that antigen processing efﬁ- ciency may decline (Lung et al 2000; Aydar et al 2004). Other laboratories have reported no major effects of aging on human peripheral blood dendritic cells when cultured in vitro with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (Steger et al 1996). In summary, aging may impact only certain types of DCs and/or their speciﬁc functions. Macrophages are another class of lymphocytes belonging to the innate immune system that serve four important roles. They (1) present antigen to memory (but not naïve) cells, produce both (2) cytokines and (3) reactive nitrogen and oxygen species, and (4) clean up cellular debris. Similar to DCs, macrophages also link innate and adaptive immunity. Some of the earlier work using macrophages from rodents tended to suggest that certain functions (ability to produce oxygen radicals in response to bacterial challenge) did not decline with age (Esposito et al 1988). Obtaining pure macrophages from humans is logistically difﬁcult, and researchers instead typically collect peripheral blood mononuclear cells (PBMCs) containing the immature progenitors of macrophages, the monocytes. Overall, immunosenescence is associated with a general decline in macrophage function (Sebastian et al 2005), possibly due to impaired ability of macrophages to respond to activation or due to a decline in activation signals from other cells. The antigen-presenting capacities of peripheral blood monocytes from older humans appears to be compromised due to alterations in MHC class II gene expression (Villanueva et al 1990), and the activities of infection-response proteins, such as heat shock proteins, may also be altered (Njemini et al 2005). In one human study that did obtain macrophages directly from the lungs, investigators found a decrease in accessory function of these cells (Zissel et al 1999). Aging has been associated with alterations in the pro- inﬂammatory/antiinﬂammatory balance. Monocytes and macrophages, as well as other cell types, can produce proin- ﬂammatory cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF)-α. Though results from numerous studies suggest that serum levels of proinﬂammatory cytokines are increased with advancing age, it is less clear whether LPS- stimulated or pathogen-induced production of IL-1, IL-6, or TNF-α by monocytes/macrophages (or both) are altered with age. For example, one study using inﬂuenza virus stimula- tion demonstrated an age-related increase in production of a proinﬂammatory cytokine (TNF-α) and a concomitant age-related decrease in production of an anti-inﬂammatory cytokine (IL-10) (Saurwein-Teissl et al 2000). When LPS rather than inﬂuenza was used as the stimulus, an age- related reduction in monocyte TNF-α and IL-6 production was reported (Delpedro 1998). In contrast, when PHA and PMA were used as costimulants, an age-related increase in TNF-α, IL-1, and IL-6 was observed (Fagiolo et al 1993). Interestingly, in another study, researchers controlled for health status of both old and young subjects and concluded that aging did not induce any differences IL-6 production after PHA or concanavalin A (ConA) stimulation, nor on TNF-α production in unstimulated monocytes (Mysliwska et al 1999; Beharka et al 2001). However, during a period of illness (pneumonia infection), both serum levels of IL-1 and IL-6 as well as production of these cytokines by LPS-stimu- lated monocytes were impaired in older adults as compared to younger adults. Additional studies are needed to clarify the impact of ag- ing on macrophage/monocyte cytokine release. This area of research is an important topic as reported by the data from a recent study of older adults, which suggested that both frailty and mortality were associated with an impaired production of pro-inﬂammatory (IL-1β, IL-6, TNF-α) and anti-inﬂamma- tory (IL-1Ra, IL-10) cytokines when LPS was used to simu- late peripheral blood mononuclear cells (van den Biggelaar et al 2004). Beyond inﬂammation itself, these results also are important for adaptive immunity. Using aged T cells from mice, researchers were able to show that the age-associated impairment of T cell proliferation and IL-2 production was reversed when cells were supplemented in vivo with IL-1, IL-6, TNF-α, or adjuvant which evoked proinﬂammatory cytokine production (Haynes et al 2004). It is likely that discrepancies in age-related responses of the monocyte or macrophage were related to either the type of stimulus or the cell source. Support for this possibility has 6 Clinical Interventions in Aging 2007:2(1)