LEUKOTRIENES IN THE PATHOPHYSIOLOGY OF KWASHIORKOR

The actions of cysteinyl leukotrienes include production of oedema. We investigated whether these mediators might be involved in the oedematous malnutrition syndrome kwashiorkor. The capacity of leukotriene (LT) synthesis by stimulated whole blood and urinary LTE4 excretion was measured in 12 children with kwashiorkor, and compared with that in 24 marasmic and 12 control children. Urinary LTE4 excretion was significantly higher in patients with kwashiorkor than in controls (118 8 [SD 28.5] vs 31.1 [19.3] nmol/mol creatinine; p<0.01). Whole blood LTE4 synthesis was increased in kwashiorkor patients by a factor of 3.5 (p<0.01). In marasmic children, LTE4 excretion and synthesis did not differ from those in controls. Although glutathione, known to participate in LTC4 synthesis, was subnormal in erythrocytes of all malnourished patients, whole-blood LTC4 synthesis was higher in kwashiorkor patients than in controls (28.1 [5.01 ng/mL; p<0.05), and close to control values (9.8 [1.51 ng/mL) in marasmic children. LTB4 synthesis, however, was greatly reduced in kwashiorkor patients (11.5 [2.4] vs 46.5 [6.4] ng/mL; p<0.01). Inability to synthesise the immunoregulator LTB4 may lead to inefficient chemoattraction of phagocytes and an inadequate inflammatory response in kwashiorkor. The increased endogenous cysteinyl LT generation in kwashiorkor suggests that these lipid mediators are involved in the pathophysiology of the syndrome, particularly in oedema formation.