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Leukotrienes in the pathophysiology of kwashiorkor
E Mayatepek1, K Becker, L Gana
1University Children's Hospital, Division of Tropical Paediatrics, Heidelberg, Germany.
Insights
Children with kwashiorkor show increased cysteinyl leukotriene (LT) generation, particularly LTE4, suggesting their role in edema. This contrasts with marasmic children, indicating a specific link to kwashiorkor pathophysiology.
Area of Science:
- Biochemistry
- Immunology
- Pediatrics
Background:
- Cysteinyl leukotrienes (LTs) are implicated in edema formation.
- Kwashiorkor is an edematous malnutrition syndrome.
- The role of LTs in kwashiorkor pathophysiology remains unclear.
Purpose of the Study:
- To investigate the involvement of leukotrienes in the pathogenesis of kwashiorkor.
- To compare leukotriene synthesis and excretion in children with kwashiorkor, marasmus, and healthy controls.
Main Methods:
- Measured leukotriene (LT) synthesis in stimulated whole blood.
- Assessed urinary LTE4 excretion.
- Compared these markers in 12 kwashiorkor, 24 marasmic, and 12 control children.
Main Results:
- Urinary LTE4 excretion and whole blood LTE4 synthesis were significantly higher in kwashiorkor patients compared to controls.
- Marasmic children showed no difference in LTE4 levels compared to controls.
- LTB4 synthesis was significantly reduced in kwashiorkor patients, while LTC4 synthesis was elevated.
Conclusions:
- Increased endogenous cysteinyl LT generation, particularly LTE4, is a feature of kwashiorkor.
- These lipid mediators likely contribute to the pathophysiology of kwashiorkor, especially edema formation.
- Reduced LTB4 synthesis may impair inflammatory responses in kwashiorkor.
Abstract:
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 [5.0] ng/mL; p < 0.05), and close to control values (9.8 [1.5] 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.