Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy

Abstract

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-y), and cytokine receptors (tumor necrosis factor receptor [TNF-R] were elevated compared with those in healthy controls (1L-6, 11.4 pg/ml; IFN-y, 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 group) who showed prolonged fever (>5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P <.05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be usefil in predicting outcome.

Host Specificity of Bacterial Pathogens

“…The pathology observed in hu-SRC-SCID mice infected with S. Typhi resembles human typhoid in a number of respects, including hepatic Kupffer cell swelling and splenic granulomatous inflammation with epithelioid macrophages and multinucleated giant cells (Mallory 1898;Ayhan et al 1973;Bharadwaj et al 2009). Elevated serum levels of the cytokines IL-6, IFN-g, and TNF-a are also observed, as in patients with typhoid fever (Butler et al 1993;Keuter et al 1994). Engraftment of human hematopoietic stem cells into a different mouse background, Rag2 IL2rg null mice, has also been shown to render mice susceptible to S. Typhi infection.…”

Influence of sex on clinical features, laboratory findings, and complications of typhoid fever.

“…This, in turn, may translate clinically into milder disease and high incidences of intestinal perforation and proven or presumed (reticulocytosis in the absence of hemolysis) occult blood loss in stool and possibly also a strong Widal O antibody response. Of note, the severity of typhoid fever is related to the levels of cytokine released as indicated above, 11 and critical to the pathogenesis of intestinal manifestations as indicated is hyperplasia of Peyer's patches 2 and antibodies against Salmonella O antigens, which include, among others, antibodies of the IgA type. 12 Hormonal influences appear to affect the course of disease since hepatitis is often more severe in girls at menarche as well as in pregnant women.…”

Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis

“…Serum levels of pyrogenic cytokines, such as TNF-␣ and IL-1␤, are elevated in typhoid fever patients compared to levels in healthy individuals (8,54) but are low compared to cytokine levels measured in the sera of patients with sepsis (35,117,120). During gram-negative sepsis, patients with high concentrations of bacteria in their blood have a worse prognosis than patients with lower concentrations of bacteria (9,18,22).…”