Influence of innate cytokine production capacity on clinical manifestation and severity of pediatric meningococcal disease.

OBJECTIVE: To analyze the role of the innate production capacity for tumor necrosis factor, interleukin-1beta, interleukin-12, and interleukin-10 in the clinical presentation and severity of meningococcal disease. DESIGN: Whole blood cultures from survivors of severe meningococcal disease obtained median 5.4 yrs after hospitalization were stimulated with meningococcal lipopolysaccharide and heat-killed Neisseria meningitidis bacteria. SETTING: Intensive care unit in academic hospital. PATIENTS: A total of 111 children were included. We classified these patients according to clinical manifestation in four groups: shock (n = 43); both shock and meningitis (n = 11); bacteremia (neither shock nor meningitis, n = 24); and distinct meningitis (n = 33). INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: The classification into four groups stratifies these patients according to disease severity. No differences in whole blood cytokine production were found between the patients in these four groups. However, within the group of patients who had presented with shock, interleukin-1beta and the interleukin-1beta/interleukin-10 ratio were negatively correlated with disease severity (R = -.35, p = .03 and R = -.33, p = .04, respectively; Pediatric Risk of Mortality score). CONCLUSIONS: Clinical manifestation of meningococcal disease cannot be explained by the innate production capacity of whole blood cultures for the cytokines tumor necrosis factor, interleukin-1beta, interleukin-10, and interleukin-12. In patients who presented with shock, a low production capacity for interleukin-1beta and a low interleukin-1beta/interleukin-10 production ratio was associated with more severe disease