INTERLEUKIN-6, GAMMA-INTERFERON, AND TUMOR-NECROSIS-FACTOR RECEPTORS IN TYPHOID-FEVER RELATED TO OUTCOME OF ANTIMICROBIAL THERAPY

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine recep tors (tumor necrosis factor receptor [TNF-R] p55 and TNF-R p75) were m easured in the plasma of 29 adult Nepalese with culture-positive typho id fever before therapy and on days 4 and 15 after start of therapy wi th either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 m g/kg of body weight per day for 14 days. Bacteriologic cure was define d as blood cultures testing negative on days 4 and 15 after start of t herapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse. Clinical and bacte riologic cures occurred in 24 patients. There were two clinical failur es, two patients who failed to complete therapy because of leukopenia, and one relapse. Mean levels before therapy were elevated compared wi th those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy. For six patients (three in each treatment g roup) who showed prolonged fever (>5 days) or relapse, mean levels of 1L-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectiv ely) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greate r than corresponding means for 23 patients who showed early defervesce nce (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml an d 2.7 ng/ml, P<.05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever an d that these concentrations can be useful in predicting outcome.