SERUM LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA), INTERLEUKIN-6 (IL-6), AND INTERLEUKIN-1-BETA (IL-1-BETA) IN DENGUE-INFECTED PATIENTS

Sensitive immunoenzymatic assays were used to study the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta 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-alpha were observed in dengue-infected children of all severity grades. The highest values of TNF-alpha 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-alpha 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-1beta 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-alpha compared with those of dengue-infected children. In some adult patients, IL-6 values increased and in all the patients, IL-1beta values were similar to those of healthy adults. Our results show an inconsistency in TNF-alpha and IL-6 production in dengue-infected patients that probably has important implications in the physiopathology of DHF/DSS.