High serum neopterin and low cytokine values may indicate a non-bacterial etiology for fever of unknown origin in neutropenic patients

Abstract

ObjectiveTo prospectively evaluate serum neopterin, a marker of cellular immune activation, in relation to blood culture findings and cytokine levels (tumor necrosis factor-α (TNF-α), interleukin (IL)–1 receptor antagonist, interferon-γ (IFN-γ), IL-6, and IL-10) at start of fever in neutropenic patients with hematologic malignancies.MethodsSerum samples were obtained during the first 24 h after start of fever in 27 episodes of febrile neutropenia seen in 22 patients.ResultsNeopterin levels increased significantly at start of fever (time 0) compared to baseline values (samples obtained within 72 h before start of fever). Neopterin levels peaked at 2–4 h after start of fever and returned to baseline levels after 12 h. At start of fever no differences in neopterin values were seen with regard to blood culture findings (i.e. blood-culture-negative (BCN) fever episodes versus Gram-positive bacteria versus Gram-negative bacteremia). In five of seven BCN fever episodes, in patients without other clinical evidence of infection, a high neopterin/low TNF-α value was observed and the correlation (r-value) between neopterin/TNF-α was negative in BCN fever episodes (–0.9; p<0.04), as opposed to the bacteremic episodes, where the correlation was positive (0.7; p<0.04).ConclusionThe results of this study show that febrile neutropenic patients are able to react with increased neopterin values, and that some BCN fever episodes are characterized by high neopterin/low cytokine values which may be due to an occult non-bacterial infection. To prospectively evaluate serum neopterin, a marker of cellular immune activation, in relation to blood culture findings and cytokine levels (tumor necrosis factor-α (TNF-α), interleukin (IL)–1 receptor antagonist, interferon-γ (IFN-γ), IL-6, and IL-10) at start of fever in neutropenic patients with hematologic malignancies. Serum samples were obtained during the first 24 h after start of fever in 27 episodes of febrile neutropenia seen in 22 patients. Neopterin levels increased significantly at start of fever (time 0) compared to baseline values (samples obtained within 72 h before start of fever). Neopterin levels peaked at 2–4 h after start of fever and returned to baseline levels after 12 h. At start of fever no differences in neopterin values were seen with regard to blood culture findings (i.e. blood-culture-negative (BCN) fever episodes versus Gram-positive bacteria versus Gram-negative bacteremia). In five of seven BCN fever episodes, in patients without other clinical evidence of infection, a high neopterin/low TNF-α value was observed and the correlation (r-value) between neopterin/TNF-α was negative in BCN fever episodes (–0.9; p<0.04), as opposed to the bacteremic episodes, where the correlation was positive (0.7; p<0.04). The results of this study show that febrile neutropenic patients are able to react with increased neopterin values, and that some BCN fever episodes are characterized by high neopterin/low cytokine values which may be due to an occult non-bacterial infection.