Elastase and granzymes during meningococcal disease in children: correlation to disease severity

Intensive Care Med. 2005 Sep;31(9):1239-47. doi: 10.1007/s00134-005-2720-3. Epub 2005 Jul 12.

Abstract

Objective: To investigate the levels of human neutrophil elastase and lymphocyte-derived granzymes A and B in relation to disease severity in children with meningococcal disease.

Design: Clinical observational cohort study.

Setting: Paediatric intensive care unit.

Patients: All patients with meningococcal disease during the study period were included.

Measurements and results: Blood sampling was done on the day of admission and on days 3 and 7. Assays for elastase and granzymes were done with ELISA. Sixty-one patients were included: 19 having distinct meningitis; 17 meningitis and shock; and 25 fulminant septicaemia. On admission levels of elastase were increased in all patients, being highest in those with fulminant septicaemia and lowest in those with distinct meningitis. Granzyme A (although marginally) and granzyme B levels were only increased in patients with shock. In 20 of the 28 patients admitted for > or = 3 days elastase decreased from admission ("rapid-decrease" group). In the remaining 8 patients, elastase started to decrease after 2 days ("slow-decrease" group). Patients of the "slow-decrease" group had a higher temperature up to day 4, needed more respiratory support (mean airway pressure in cm H2O on days 3 and 4: p=0.02 and p<0.01, respectively), and more circulatory support (>2 inotropic agents on day 3; p=0.04) compared with the "rapid-decrease" group.

Conclusions: Human neutrophil elastase and granzyme B are related with disease severity during the initial phase of meningococcal disease and prolonged neutrophil activation is associated with the extent of organ dysfunction during the period thereafter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granzymes
  • Humans
  • Intensive Care Units, Pediatric
  • Leukocyte Elastase / blood*
  • Male
  • Meningococcal Infections / classification
  • Meningococcal Infections / enzymology*
  • Prospective Studies
  • Serine Endopeptidases / blood*
  • Severity of Illness Index

Substances

  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • Leukocyte Elastase
  • GZMA protein, human