Changes in the interleukin-6/soluble interleukin-6 receptor axis in meningococcal septic shock.

OBJECTIVE: Interleukin-6 is strongly associated with disease severity and outcome in meningococcal septicemia. It is known that interleukin-6 exerts many of its effects via the soluble interleukin-6 receptor. By facilitating the activity of interleukin-6, it is likely that alterations in the levels of soluble interleukin-6 receptor in septic shock could affect the severity of disease. We aimed to investigate changes in the levels of interleukin-6 and soluble interleukin-6 receptor in acute meningococcal septicemia and the relationship with disease severity.

DESIGN: Laboratory investigation of interleukin-6 and soluble interleukin-6 receptor levels in children with meningococcal disease.

SETTING: University hospital and laboratories.

SUBJECTS: Children with severe meningococcal disease requiring intensive care.

INTERVENTIONS: Blood samples obtained on admission to the intensive care unit were analyzed for interleukin-6 and soluble interleukin-6 receptor levels. Levels were also serially measured for up to 48 hrs in a subset of patients.

MEASUREMENTS AND MAIN RESULTS: Cytokine levels were measured by enzyme-linked immunosorbent assay using mouse monoclonal antihuman antibodies. Acute meningococcemia is associated with a reduction in soluble interleukin-6 receptor levels in proportion to disease severity and is inversely related to interleukin-6 levels. Soluble interleukin-6 receptor returns to levels seen in normal donors following recovery from meningococcal septicemia.

CONCLUSIONS: Changes in the levels of interleukin-6 and soluble interleukin-6 receptor in acute meningococcemia may affect the severity and progression of multiple organ failure. Interventions to modulate this axis may improve outcome from meningococcal septic shock.