Cytokine profile in Typhoid fever: Correlation with clinical features and sensitivity patterns

We have previously reported significant elevation of serum interleukin (IL)-6 and tumor necrosis factor (TNF) - α concentrations in typhoid fever and a relationship with relapse rates. In the present study we prospectively evaluated admission plasma concentration of pro-inflammatory cytokines IL-Iβ, IL-6 and TNF-α as well as IL-I receptor antagonist (IL-lra), soluble IL-6 receptor (IL-6sR) and soluble TNF p55 receptor (sTNF p55r) in children with culture-proven typhoid. In comparison with a control group of children with non-typhoidal bacterial infections and febrile illnesses, children with culture proven typhoid had significantly elevated concentrations of IL-I and IL-6 at admission whereas values for TNF-α were comparable. However, children with proven typhoid also had higher concentrations of sTNFp55r and IL-lra but not IL-6sR at admission. In general, in comparison with sensitive-typhoid, children with MDR ty-phoid were more severely ill with significantly higher admission plasma C-reactive protein (83#66 versus 51#45 mg/L, p<0.05) and had comparatively higher admission concentrations of IL-6; IL-Ira and sTNFp55r. Plasma cytokine concentrations correlated most closely with clinical toxicity at admission and reduced significantly by 72 hours of antimicrobial therapy. Our data indicate that in comparison with sensitive strains of typhoid, MDR typhoid is a more severe illness in childhood with greater clinical toxicity and systemic cytokine response. This may account for the comparatively slower response to therapy and defervescence as well as higher rates of adverse outcome in these children.