• Top
• Background
• Materials and methods
• Results
• Conclusion

Background

Resistin has recently been recognized to act as a proinflammatory cytokine in humans. Patients with severe sepsis or septic shock had significantly elevated systemic levels of resistin, which correlated with severity of disease. Here we have further characterized the release of resistin during severe bacterial infections.

Materials and methods

Acute phase sera collected from patients with septic shock caused by Gram-negative (n = 19) or Gram-positive (n = 19) bacteria were analyzed for resistin by ELISA. Tissue biopsies (n = 12) from patients with Streptococcus pyogenes severe soft tissue infections were stained for resistin and cell markers, and were analyzed by confocal microscopy. Human neutrophils were stimulated with lipopolysaccharide or streptococcal superantigens, and resistin was assessed in the supernatants.

Results

Serum resistin levels were significantly elevated in patients with Gram-positive, as compared with Gram-negative, septic shock (P = 0.004). Analyses of tissue biopsies revealed that resistin was highly expressed at the local site of infection. Dual-staining for cell markers confirmed published findings that monocytes are a source of resistin in humans, but importantly the stainings revealed that the majority of resistin-producing cells were negative for the monocytic marker CD68. Further analyses identified these cells as neutrophils. A positive correlation between resistin levels and neutrophil counts was found in blood of septic shock patients (P = 0.005). In vitro cell cultures revealed resistin release by neutrophils stimulated with lipopolysaccharide or superantigens.

Conclusion

This study demonstrates that the systemic resistin levels in septic shock differ depending on the causative microorganisms. The data also reveal that, at the local tissue site of infection, resistin is produced mainly by neutrophils, and systemic resistin strongly correlates with circulating levels of neutrophils. The systemic and local hyper-resistinemia noted is likely to contribute to the pathogenesis of acute invasive bacterial infections.

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