Intravenous administration to volunteers of an emulsion of medium-chain lipids, but not of an emulsion of pure long-chain lipids or a placebo, increased the growth of Candida albicans in serum and modulated Candida-induced cytokine production by mononuclear cells in a way suggesting that medium-chain, but not long-chain, triglycerides increase the risk for infections by Candida.The provision of total parenteral nutrition (TPN) is an indispensable strategy to improve the nutritional status of critically ill patients. However, altered immune responses by the TPN lipid component may contribute to the increased rate of infectious complications for these patients (43). It remains unclear whether structurally different lipid emulsions containing either pure long-chain triglycerides (LCT) or mixed longand medium-chain triglycerides (LCT-MCT) exert distinct immune-modulating effects (1, 3, 4, 7, 8, 10, 12-15, 18, 25, 27, 28, 32, 33, 35-37, 40, 42, 43, 44). Recently, we found that LCT-MCT, unlike LCT, increase in vitro oxygen radical production and adhesion of neutrophils but decrease cellular motility and killing of Candida albicans (20,(45)(46)(47)(48). This observation is important because clinical studies indicate that 5% of all patients receiving TPN develop candidemia, with significant mortality and morbidity (38).In the present study, we exposed LCT and LCT-MCT to the metabolisms and immune systems of healthy volunteers. We investigated the effects of lipids on two pathogenetic aspects of Candida infections: yeast growth and the balance of proinflammatory (gamma interferon [␥-IFN], tumor necrosis factor alpha [TNF-␣], interleukin-1 , and IL-6) and anti-inflammatory (IL-10) cytokines (2,19,29,30,34,41).Emulsions containing LCT, LCT-MCT, or saline were administered during 4 h to eight volunteers in a study with a crossover design and a 1-week washout period. Blood samples were taken before and after 4 h of lipid or placebo administration and analyzed as described below. In order to stabilize plasma triglyceride concentrations at a clinically relevant concentration of 3 to 5 mmol/liter, emulsions (overall, ca. 220 ml) were infused according to a triglyceride-clamp schedule (16,17). For emulsion characteristics, see Table 1.Leukocytes were isolated from 20 ml of blood anticoagulated with lithium-heparin (6,21,45). Peripheral blood mononuclear cells (PBMC) were removed and suspended in medium (RPMI 1640 DM; Flow Laboratories, Irvine, United Kingdom). Heat-killed C. albicans (strain UC820; final concentration, 10 7 CFU/ml) was used for ex vivo PBMC stimulation in the cytokine assays. After PBMC isolation, cell numbers were adjusted (5 ϫ 10 6 /ml) and cell suspension samples were incubated with Candida (24 h, 37°C). After incubation, the supernatants were frozen (Ϫ20°C) until assayed. IL-1 and TNF-␣ (both in nanograms per milliliter) in supernatants were measured by radioimmunoassays as described previously (23). Detection limits of the assay were 20 pg/ml for TNF-␣ and 40 pg/ml for IL-1. Interassay variation was les...