The immune response after stimulation with wall components of gram-positive bacteria and fungi

• Lipoteichoic acid and mannan are potent immunostimulators.
• ICU non septic patients are in a profound inflammatory state.
• ICU non septic patients show immune cell exhaustion comparable to immunoparalysis.
• Chronic renal and diabetic patients show an adequate response to immunostimulation.

Although several components of the microbial wall of gram-positive bacteria and fungi possess immunostimulatory properties, their pathogenetic role remains incompletely evaluated. The purpose of this study was to assess the basic immune status of patients susceptible to infections and their capability for cytokine production after stimulation with wall components of gram-positive bacteria and fungi. We measured serum cytokine levels as well as cytokine production after ex vivo lipoteichoic acid (LTA) and mannan stimulation of whole blood. The blood was taken from 10 healthy volunteers, 10 patients with end-stage renal disease (ESRD), 10 patients with diabetes mellitus (DM), and 10 patients on their 2nd day of stay in the Intensive Care Unit (ICU), who suffered from non septic systemic inflammatory response syndrome (SIRS) and had an APACHE II score ≥25. We used 1 μg/ml LTA and 100 μg/ml mannan for an incubation period of 8 h to stimulate 100 μl aliquots of whole blood. All patient groups had higher baseline values of TNF-α, IL-6, IL-1β, and IL-10 compared to the control group, but only for ICU patients the difference was statistically significant. The ratio IL-10/IL-6 was found 0.33, 0.22, and 0.96 in healthy persons, ESRD, and DM patients respectively, and 1.32 in ICU patients. In all examined groups, the levels of cytokines significantly increased after stimulation by LTA and mannan, although in severely ill patients this change was considerably smaller, possibly reflecting a state of monocytes’ depression and relative hyporesponsiveness. No significant differences between the LTA and the mannan stimulation were observed.