Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: a case–control study

Abstract

Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively). Conclusion We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Risk-score based strategy to minimize antibiotic exposure in children with sickle cell disease and fever

“…Most children included in this study had been diagnosed by newborn screening, were completely immunized and receiving penicillin prophylaxis. We found a low rate of CSBI, with a higher proportion of PSBI (mainly pneumonia/ACS), in agreement to other studies from high-income countries [1,3,6]. Several studies had previously reported different predictors of bacteremia and other severe infections in patients with SCD, including elevated CRP, procalcitonin, WBC and neutrophils, toxic appearance, vomiting and longterm CVC, similarly to our findings [2,4,7,8].…”

Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review

“…TNF- is crucial to understanding the pathogenesis of RA. The expression of serum TNF- may make early RA more inflammatory [ 147 ]. As a result, it is necessary to test patients with RA for this cytokine to keep track of disease activity, which may be helpful for patients who are undergoing anti-TNF therapy.…”

Future Biomarkers for Infection and Inflammation in Rheumatoid Arthritis

“… 22 Early elevation of IL-6 in the presence of SBI, is an important advantage of this cytokine compared with other biomarkers. 23 IL-6 plays a significant role in inducing CRP and fibrinogen synthesis in the liver during bacterial infection.…”

“…The expression of serum TNF-α may enhance the inflammatory activity of early RA. 23 Therefore, RA patients must be screened for this cytokine to monitor disease activity, which may be useful in patients receiving anti-TNF therapy. TNF-α itself is a potent inducer of other proinflammatory cytokines and chemokines, further enhancing the inflammatory response.…”