Patterns of proinflammatory cytokines and inhibitors during typhoid fever

Cytokines and inhibitors in plasma were measured in 44 patients with typhoid fever. Ex vivo production of the cytokines was analyzed in a whole blood culture system with and without lipopolysaccharide (LPS). Acute phase circulating concentrations of cytokines (+/- SD) were as follows: interleukin (IL)-1 beta, < 140 pg/mL; tumor necrosis factor-alpha (TNF alpha), 130 +/- 50 pg/mL; IL-6, 96 +/- 131 pg/mL; and IL-8, 278 +/- 293 pg/mL. Circulating inhibitors were elevated in the acute phase: IL-1 receptor antagonist (IL-1RA) was 2304 +/- 1427 pg/mL and soluble TNF receptors 55 and 75 were 4973 +/- 2644 pg/mL and 22,865 +/- 15,143 pg/mL, respectively. LPS-stimulated production of cytokines was lower during the acute phase than during convalescence (mean values: IL-1 beta, 2547 vs. 6576 pg/mL; TNF alpha, 2609 vs. 6338 pg/mL; IL-6, 2416 vs. 7713 pg/mL). LPS-stimulated production of IL-1RA was higher in the acute than during the convalescent phase (5608 vs. 3977 pg/mL). Inhibited production of cytokines during the acute phase may be due to a switch from a proinflammatory to an antiinflammatory mode.