Cytokine Profiles in Children with Primary Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome

Abstract

Primary hemophagocytic lymphohistiocytosis (pHLH) and macrophage activation syndrome (MAS) are the 2 fatal hyperinflammatory disorders sharing similar clinical features and underlying pathogenic mechanisms. The present study aimed to assess the cytokine profiles in these children and to ascertain whether specific cytokines correlate with specific laboratory parameters. We enrolled 10 pHLH and 10 MAS patients. Serum levels of cytokines, including IL-6, IL-8, IL-10, IFN-γ, IL-1β, IL-18, and TNF-α, were measured in each patient and compared with age-matched controls. IL-18 and IL-10 were the 2 cytokines that were most significantly elevated in pHLH (P value < 0.001 and P value = 0.0011, respectively), while IL-8 was considerably lower than controls (P value = 0.0054). In MAS patients, IL-18 (P value = <0.002), IL-10 (P value = 0.0030), and IL-6 (P value = 0.028) were the 3 most significantly elevated cytokines. Specific cytokines were found to correlate significantly with ferritin, triglycerides, fibrinogen, platelet count, hemoglobin, absolute neutrophil count, and absolute monocyte count. Overall, IL-18 and IL-10 are the most consistently elevated cytokines in both pHLH and MAS, while IL-6 is uniquely elevated in MAS. Cytokines not only play a role in the HLH pathophysiology but may also serve as disease biomarkers.