Serum Levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β) in Dengue-Infected Patients

Abstract

Sensitive immunoenzymatic assays were used to study the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in sera from dengue-infected patients obtained during the 1989–1990 outbreak of dengue-3 in Tahiti, French Polynesia. The patients, both children (n = 47) and adults (n = 18), were clinically classified as having dengue hemorrhagic fever (DHF) and graded according to the severity of illness (grade I = fever, grade II = fever with spontaneous hemorrhagic manifestations, grade III = circulatory failure, grade IV = deep shock). The serum samples were obtained from day 1 to day 10 after the onset of the disease. High levels of TNF-α were observed in dengue-infected children of all severity grades. The highest values of TNF-α were found before day 6 after the onset of the infection, these values decreased from day 6 to day 10. The highest values were observed in sera from grade III and IV patients. High values of IL-6 were observed in serum samples of grade I and II patients on day 1, which decreased on day 4, and by day 5 were similar to those obtained from 25 control children. In grade III and IV patients, the highest values of IL-6 were observed from day 3 to day 5 after the onset of infection; after day 5, these values were very low. The highest values of IL-6 in grade III patients were accompanied by elevated values of TNF-α and were observed in serum obtained on the day the patient went into shock (dengue shock syndrome [DSS]). The IL-6 values were normal one day before and one day after the patient went into shock. The values of IL-1β were similar to those of 25 control children. Serum samples from dengue-infected adults, obtained from day 4 to day 10 after the onset of disease, showed moderately high levels of TNF-α compared with those of dengue-infected children. In some adult patients, IL-6 values increased and in all the patients, IL-1β values were similar to those of healthy adults. Our results show an inconsistency in TNF-α and IL-6 production in dengue-infected patients that probably has important implications in the physiopathology of DHF/DSS.