Selective expansion of the CD14⁺/CD16^bright subpopulation of circulating monocytes in patients with hemophagocytic syndrome

Overproduction of proinflammatory cytokines is characteristic of hemophagocytic syndrome (HPS), a highly lethal inflammatory disease. Peripheral blood monocytes include two distinct subpopulations according to surface antigen expression: a major type, CD14⁺/CD16⁻ (classical monocytes), and a minor type, CD14⁺/CD16^bright (proinflammatory monocytes). Among peripheral blood monocytes from HPS patients, CD14⁺/CD16^bright cells were increased, together with lipopolysaccharide-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. By three-color immunofluorescence, CD14⁺/CD16^bright monocytes exhibited more intense human leukocytic antigen DR than CD14⁺/CD16⁻ monocytes, consistent with greater maturity. Serum IL-6, TNF-α, and IL-8 were increased in HPS patients. A sensitive inflammatory marker, neutrophil CD64 expression, also was significantly elevated in HPS patients. In conclusion, expansion of proinflammatory monocytes and increased expression of neutrophil CD64 appeared to be important in the pathophysiology of HPS. Expansion of CD14⁺/CD16^bright monocytes and neutrophil CD64 expression could serve as indicators of the inflammatory state in HPS.