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

Abstract

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 +/- 1 years, mean +/- SEM) and 12 healthy age-matched controls were examined. MAIN OUTCOME MEASURES: Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed cutaneous hypersensitivity (DCH) reaction were determined. RESULTS: BMI was 16. 5 +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- 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 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 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.