Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly

Objective. The dysregulation of the immune and inflammatory systems observe d in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium io nophore A23187-induced generation of the arachidonate metabolites leukotrie ne 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-m alignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-ma tched controls were examined. Main outcome measures. Leukotrienes were analysed by high-performance liqui d chromatography. Body mass index (BMI, kg m(-2)) and delayed cutaneous hyp ersensitivity (DCH) reaction were determined. Results. BMI was 16.5 +/- 0.5 and 26.2 +/- 0.9 kg m(-2) (mean +/- SE) in th e 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 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL(-1), P < 0.05) when cells were stimulated with 0. 2 mu mol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL(-1), resp ectively (NS), upon stimulation with 1.0 mu mol L-1 of A23187. LTB4 product ion in PEM patients and controls did not differ at any of the two calcium i onophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LT C4 production. Conclusion. Protein-energy malnutrition is accompanied by perturbation of l eukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.