HMGB1 expression in streptococcal soft-tissue infections correlates with disease severity
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KeywordsDisease Severity Cellulitis Fasciitis Inflammatory Cell Infiltration Bacterial Load
High mobility group box-1 (HMGB1) is an intracellular protein that is secreted by activated immune cells during inflammation, or is passively released by cells undergoing necrosis. HMGB1 acts both as a proinflammatory cytokine and a chemokine, and has been identified as a late mediator of sepsis. We have studied HMGB1 expression in streptococcal skin and soft-tissue infections, and its relation to bacterial load as well as to infiltration of inflammatory cells.
Materials and methods
Thirty-seven biopsies from 17 patients suffering from streptococcal skin and soft-tissue infection were obtained and graded according to disease severity (erysipelas, cellulitis, necrotizing fasciitis). Three additional biopsies served as negative controls. Tissue sections were immunostained for HMGB1, group A streptococcus, and specific cell markers. Sections were investigated by light microscopy, and results were quantified by in situ imaging.
HMGB1 was found both intracellularly and secreted in the tissue. Its expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (P = 0.023). HMGB1 showed a positive correlation to neutrophils (P < 0.01) in erysipelas, but not in severe infections. A correlation to bacterial load was not found.
In contrast to erysipelas, large amounts of necrotic tissue are present in severe skin infections, which probably contribute considerably to the expression of HMGB1. The high values may disturb a statistical correlation to the degree of inflammatory cell infiltration in the tissue. However, our results suggest that the massive HMGB1 expression at the local site of infection is probably an important mediator and enhancer of inflammation in skin tissue and soft-tissue infections, as evident by its expression in correlation to disease severity.