Abstract. Cederholm T, Lindgren JA Ê , Palmblad J (Centre for Hematology and Inflammatory Research, Huddinge University Hospital and Karolinska Institutet, Stockholm, Sweden). Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly. J Intern Med 2000; 247: 715±722.Objective. The dysregulation of the immune and inflammatory systems observed in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187-induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions. Design. Case±control study. Setting. A university-affiliated acute care hospital in urban Stockholm. Subjects. Fourteen severely malnourished elderly subjects with stable non-malignant disorders (age 74 6 1 years, mean 6 SEM) and 12 healthy agematched controls were examined. Main outcome measures. Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m 22 ) and delayed cutaneous hypersensitivity (DCH) reaction were determined.Results. BMI was 16.5 6 0.5 and 26.2 6 0.9 kg m 22 (mean 6 SE) in the malnourished group and controls (P , 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P , 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 6 2.0 vs. 17.8 6 5.2 pmol mL 21 , P , 0.05) when cells were stimulated with 0.2 mmol L 21 of A23187, and 13.7 6 2.5 and 27.2 6 7.5 pmol mL 21 , respectively (NS), upon stimulation with 1.0 mmol L 21 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P , 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production. Conclusion. Protein-energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.