Related Experiment Videos
Impairment of polymorphonuclear leucocyte function during therapy with synthetic ACTH in children affected by
Insights
Synthetic ACTH therapy for epileptic encephalopathy in children significantly reduces polymorphonuclear leucocyte (PMN) phagocytic activity, increasing infection risk. Alternate-day ACTH may mitigate these effects, suggesting a safer treatment approach.
Area of Science:
- Pediatric Neurology
- Immunology
- Pharmacology
Background:
- Synthetic adrenocorticotropic hormone (ACTH), specifically zinc tetracosactide, is used to treat epileptic encephalopathies like West syndrome and Lennox-Gastaut syndrome in children.
- This therapy is frequently linked to an increased incidence of infectious complications in pediatric patients.
Purpose of the Study:
- To investigate the impact of synthetic ACTH (zinc tetracosactide) on the phagocytic activity of polymorphonuclear leucocytes (PMN) in children with West or Lennox-Gastaut syndrome.
- To evaluate the relationship between altered PMN function and the occurrence of infectious episodes during ACTH therapy.
- To compare the efficacy and safety of daily versus alternate-day ACTH administration.
Main Methods:
- Studied 9 children with West or Lennox-Gastaut syndrome undergoing zinc tetracosactide therapy.
- Measured PMN superoxide anion production during Zymosan particle phagocytosis and after phorbol myristate acetate (PMA) stimulation.
- Assessed phagocytic function before, during, and after a 15-day course of zinc tetracosactide (0.02 mg/kg/day); also measured plasma immunoglobulins, complement components (C3, C4, C3 activator), and cortisol.
Main Results:
- PMN phagocytic function was significantly impaired during daily synthetic ACTH treatment but normalized after therapy cessation.
- Fifteen infectious episodes were observed, including candidiasis, enterocolitis, urinary tract infections, otitis media, bronchiolitis, and pneumonia; one patient died from pneumonia.
- Children receiving alternate-day ACTH showed less impaired PMN activity and fewer infections.
Conclusions:
- Daily synthetic ACTH therapy in children with epileptic encephalopathy suppresses PMN phagocytic function, contributing to increased susceptibility to infections.
- Alternate-day ACTH administration appears to be a potentially safer therapeutic strategy, with reduced impairment of immune function and fewer infectious complications.
- Further research into optimizing ACTH dosing regimens is warranted to balance efficacy and minimize infectious risks in pediatric epilepsy treatment.
Abstract:
Therapy with synthetic ACTH (zinc tetracosactide) in children affected by epileptic encephalopathy is often associated with a large number of infectious complications. We studied the phagocytic activity of polymorphonuclear leucocytes (PMN) in 9 children with West or Lennox-Gastaut syndrome, measuring PMN superoxide anion production during the phagocytosis of particles of Zymosan and after phorbol myristate acetate (PMA) stimulation. The test was performed before, during and after therapy with zinc tetracosactide (0.02 mg/kg/day for 15 days). At the same time plasma immunoglobulins, C3, C4, C3 activator and cortisol were determined. During treatment PMN phagocytic function was significantly reduced but returned to normal levels after suspension of therapy. The other hematological parameters considered remained within the normal range. During the follow-up of the patients we observed 15 infectious episodes (3 mucocutaneous candidiasis, 2 enterocolitis, 4 urinary tract infections, 1 otitis media, 3 bronchiolitis, 2 pneumonia). One of the patients died of a bilateral pneumonia. Three children were treated with ACTH on alternating days. In these patients PMN phagocytic activity was less impaired and 2 infectious episodes rapidly resolved. Alternate day ACTH therapy seems to be preferable.