Volume 3 Supplement 1
A novel explanation for profound shock in meningococcal sepsis
© Current Science Ltd 1999
Published: 16 March 2000
A principle feature of gram negative sepsis is the rapid onset of profound shock. The failure of anti-endotoxin antibodies to produce significant improvement in outcome  and the profound hypocalcaemia we have observed in meningococcal sepsis led us to re-evaluate the possible aetiologies of shock in Gram negative infection.
To test the hypothesis that Gram negative organisms directly or indirectly may he capable of proteolycic breakdown of albumin thus explaining in part the aetiology of shock and hypocalcaemia seen in severe Gram negative sepsis.
Urine was collected from patients with severe meningococcal sepsis (11) and from controls including patients admitted to intensive care (2) and patients with known proteinuria (4). The urine was dialysed and subjected to polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with a sheep antihuman albumin antibody.
Albumin was incubated with lipopolysaccharide (LPS) derived from various Gram negative organisms and the incubates were subjected to SDS-PAGE to ascertain the presence of albumin degradation products. Albumin was also incubated with homogenates of cultured Neisseria meningitidis and again the incubates were subjected to SDS-PAGE.
Multiple albumin fragments were detected in urine collected from patients with meningococcal sepsis. In vitro incubation of human albumin with crude LPS denied from gram negative organisms and subsequent SDS-PAGE also showed cleavage of albumin into multiple fragments. Similar in vitro studies with homogenates of N. meningitidis failed to show evidence of breakdown. No albumin cleavage products were detected in the urine of control patients.
This study suggests that in meningococcal sepsis there is release into the circulation of protease(s) which cleave albumin. We were not able to distinguish whether the protease action was of exogenous or endogenous origin. This may have profound significance for the treatment of meningococcal sepsis.
- The HA-1A Sepsis Study Group: Treatment of gram negative bacteraemia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomised, double blind placebo-controlled trial. N Engl J Med 1991, 324: 429-436. Brussels, Belgium. 16-19 March 1999