An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients

A prospective study was performed to assess the potential value of interleukin (IL)-8, IL-6, and C-reactive protein (CRP) serum levels to predict fever, gram-negative bacteremia and complicated infection in neutropenic patients with cancer. Serum samples were obtained three times a week during 208 neutropenic episodes following cytotoxic chemotherapy. Fever of any cause developed during 104 out of 191 evaluable episodes. Serum levels of neither cytokine nor CRP were predictive of fever within more than 24 h before its onset. Unlike CRP, both IL-6 and IL-8 serum levels were significantly different between microbiologically documented infections and unexplained fevers. The highest values of IL-6 and IL-8 were observed in episodes of gram-negative bacteremia. Using receiver-operating-characteristic curves, the analysis of cytokine levels measured around the onset of fever indicated that IL-8 is potentially useful for predicting gram-negative bacteremia, with a high negative predictive value of > 90% and a moderate positive predictive value of 50% (sensitivity, 70%; specificity, 91%). In patients with persistent fever, predictions of further clinical complications, defined as prolonged fever of more than 7 days' duration, pneumonia, shock and/or death due to infection, were best predicted by IL-6. With an IL-6 cutoff value of 250 pg/ml in samples obtained 8 to 32 h after onset of fever, the positive predictive value was 92%, the negative predictive value 91% (sensitivity, 85%; specificity, 95%). The positive predictive value of IL-6 in samples obtained another 24 h later from patients still febrile remained > 90%, but the negative predictive value dropped to 47%. In any of the analyses, the predictive values of CRP levels were poor and inferior to either cytokine. These findings may have clinical value in identifying subgroups of patients requiring different therapeutic approaches.