Context: Neutrophil (PMN) production of leukotriene B₄ (LTB₄), may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS).

Objective: We investigated whether PMN production of LTB₄ and its metabolites 20-OH-LTB₄ and 20-COOH-LTB₄ were altered in subjects with features of the MetS before and after weight reduction.

Design, Setting, Patients, and Intervention: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16 wk of weight maintenance.

Main Outcome Measures: Measurements were performed at baseline and the end of the 16-wk period. Stimulated neutrophil LTB₄ and its metabolites were measured by HPLC.

Results: In the case-controlled study, BMI, waist circumference, blood pressure, fasting triglycerides and glucose were all significantly raised in subjects with features of the MetS (P < 0.05). Production of LTB₄ and 20-OH-LTB₄ was significantly lower compared with controls (P < 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB₄ and 20-OH- LTB₄.

Conclusion: Subjects with features of the MetS have lower stimulated LTB₄, which is not due to increased metabolism of LTB₄. Weight reduction restored the production of neutrophil LTB₄, suggesting that as well as modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.