Interleukin-6 concentrations in wound fluids rather than serological markers are useful in assessing bacterial triggers of ulcer inflammation

Abstract

Bacterial pathogenicity, microbial load and diversity are decisive for outcome and therapy of non healing ulcers. However, until now, no routine laboratory parameter is available to assess the inflammatory level caused by chronic wound infections. We thus investigated the usefulness of levels of interleukin (IL)-6 and tumour necrosis factor alpha (TNFalpha) in wound fluids for assessing ulcer inflammation in the presence or absence of microbial triggers. In addition, the predictive values of local cytokine analyses were compared with those of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) because serological markers are normally used to underline the suspicion of wound infections. The present data from chronic arterial and venous ulcers (n = 45) clearly show that mixed bacterial infections increased IL-6 and TNFalpha concentrations in wound fluids when compared with ulcers with a monomicrobial infection (P < 0.01 and P < 0.05, respectively). IL-6 was also significantly elevated when a high bacterial load [versus <10(5) colony-forming units (cfu)/ml: P = 0.04] or an infection with Pseudomonas was observed (versus isolation of non Pseudomonas strains: P = 0.05). Although distinct proinflammatory triggers may interfere with regard to cytokine levels, sensitivity and specificity were significant in predicting bacterial risk factors, particularly for IL-6 at a designated cut-off of 125 pg/ml (sensitivity and specificity for predicting a mixed infection: 70% and 64%, for predicting a bacterial load of >10(5) cfu/ml: 62% and 57% and for predicting an infection with Pseudomonas: 90% and 57%). In contrast to local cytokine levels, the serological markers CRP and LBP were not associated with the presence of any of the investigated bacterial triggers. Focusing on the aim of the study, IL-6 analysed in wound washouts seems to be a useful diagnostic marker for a sensitive and specific assessment of ulcers inflammation with regard to bacterial triggers.

Wound Fluid Diagnostics in Diabetic Foot Ulcers

“…Nevertheless, in neuropathic diabetic foot ulcers the healing rate was also found to be inversely correlated with high bacterial loads (Xu et al 2007). Furthermore, in a study by Ambrosch et al, a good correlation between local CRP and TNF levels in wound washouts and tissue punch biopsies could be shown (Ambrosch et al 2008). …”

“…The analysis of local IL-6 and TNF was shown to be able to discriminate between monomicrobial and polymicrobial infections in contrast to serum CRP and liposaccharide binding protein (LBP). Furthermore, local IL-6 was reported to reflect higher bacterial loads and infection, especially with pseudomonas (Ambrosch et al 2008). The determination of CRP as well as LBP as serological parameters, together with the semi-quantitative analysis of bacterial load and microbial identification, was performed.…”

“…To overcome the obstacles of methodological limitations in sample material and sampling difficulties, a technique using washouts of wound areas by the application of 5ml of sterile saline to wounds and subsequent collection of the fluid again by needle aspiration has been proposed (Ambrosch et al 2008). However, a relevant dilution of the sample may again occur and so exert undetermined effects on the original fluid matrix.…”

Does Inflammation Have a Role in the Pathogenesis of Venous Ulcers?: A Critical Review of the Evidence

“…These data suggested that the initiation of healing was not followed by a significant change in the level of bioactive TNF-a, and that the level of TNF-a may not be the main regulator of healing in chronic venous ulcers. Ambrosch et al (2008) showed that venous ulcers with mixed bacterial infection had increased TNF-a levels compared with monomicrobial infection, suggesting that elevation of TNF-a may also correlate with severity of infection.…”

Advances in Infections and Wound Healing for the Diabetic Foot

“…Despite the pilot design, this work opens new perspectives for the study of foot infections at the molecular level, which is becoming an evolving field. [14][15][16] Equally interesting is the role of MRSA genetic factors in foot infection with this pathogen. 17 Wang et al 18 have examined risk and genetic factors in 429 patients hospitalized with diabetic foot infection.…”