Circulating Inflammatory Mediators during Start of Fever in Differential Diagnosis of Gram-Negative and Gram-Positive Infections in Leukopenic Rats

Abstract

Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.

Lipoprotein Lipase and Hydrofluoric Acid Deactivate Both Bacterial Lipoproteins and Lipoteichoic Acids, but Platelet-Activating Factor-Acetylhydrolase Degrades Only Lipoteichoic Acids

“…In bacterial sepsis, the innate immune system provides both the initial immune responses and the early inflammatory responses (1,8,12). Early responses to infections with Grϩ and GrϪ bacteria have been shown in previous studies to involve different cytokine profiles (9,16,25,51,54). Other studies have found that infections with GrϪ bacteria activate Toll-like receptor 4 (TLR4) primarily with lipopolysaccharide (LPS), a membrane component of GrϪ bacteria (26,27,44,53).…”

Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

“…For example, the peptidoglycan by product muramyl dipeptide (MDP) is a key element in the immune response to Grampositive bacteria which lack LPS (Tavares et al, 2005). In contrast to LPS, the response to MDP is CD14-independent, and is recognized by nucleotide-binding oligomerization domain 2 (NOD2) but not "Toll-like" receptors such as LPS (Girardin et al, 2003).…”

Procalcitonin, c-reactive protein, leukocyte, mean platelet volume levels in bloodstream infections

“…The PCT elevation could be, at least in part, related to the characteristics of the pathogen in the systemic bacterial infection. It has been shown in vitro that PCT value was significantly higher in the supernatants of cultured human cells stimulated with LPS than in those stimulated with muramyl dipeptide, a component of the outer membrane of the GP bacteria [12]. In a study, the positive value of PCT in the bacterial infection rate was much higher than that of CRP and WBC, and the difference had a statistical significance (p<0.05).…”