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Local and systemic concentrations of tumour necrosis factor-alpha, interleukin-6 and interleukin-8 in bacterial
S Fullilove1, J Jellis, S P Hughes
1Department of Orthopaedic, Imperial College of Science, Technology and Medicine, London, UK.
Abstract:
Osteomyelitis is a major cause of morbidity worldwide but there are few data investigating pathogenesis of infection and no investigations into local secretion of proinflammatory cytokines in patients. Tumour necrosis factor-alpha (TNF), interleukin (IL)-6 and IL-8 concentrations were measured in pus of infected bone from 30 Zambian patients with chronic osteomyelitis (principally caused by Staphylococcus aureus), in plasma, and after lipopolysaccharide stimulation of whole-blood leucocytes. Patients had reduced body mass index compared to controls (P = 0.025) and an acute-phase response. Elevated concentrations of proinflammatory cytokines were detected in bone compared to plasma (all P < 0.0002). Bone IL-8 concentrations were greater than IL-8 levels after lipopolysaccharide stimulation of whole blood (P < 0.01). In contrast, systemic and ex-vivo-stimulated concentrations of proinflammatory cytokine were similar in patients and controls, despite differences in body mass index and an acute-phase response. In summary, we observed marked local TNF, IL-6 and IL-8 secretion in established bacterial osteomyelitis without systemic cytokine release.
Insights
This study found high levels of local inflammatory cytokines in bone infections (osteomyelitis) but not in the blood. This suggests targeted treatment strategies are needed for bone infections.
Area of Science:
- Immunology
- Infectious Diseases
- Orthopedics
Background:
- Osteomyelitis is a significant global health issue with limited understanding of its pathogenesis.
- Previous research has not investigated the local secretion of pro-inflammatory cytokines in osteomyelitis patients.
Purpose of the Study:
- To investigate the concentrations of tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the pus of infected bone in patients with chronic osteomyelitis.
- To compare local cytokine levels with plasma concentrations and ex-vivo lipopolysaccharide-stimulated whole-blood leucocyte responses.
Main Methods:
- Measurement of TNF, IL-6, and IL-8 concentrations in bone pus, plasma, and lipopolysaccharide-stimulated whole-blood leucocytes from 30 Zambian patients with chronic osteomyelitis.
- Comparison of cytokine levels between patients and controls, considering body mass index and acute-phase response.
Main Results:
- Patients exhibited reduced body mass index and an acute-phase response compared to controls.
- Significantly elevated concentrations of pro-inflammatory cytokines (TNF, IL-6, IL-8) were detected in bone pus compared to plasma.
- Bone IL-8 levels were higher than those observed after ex-vivo lipopolysaccharide stimulation, while systemic and stimulated cytokine levels were similar between patients and controls.
Conclusions:
- Established bacterial osteomyelitis is characterized by marked local secretion of TNF, IL-6, and IL-8 within the infected bone.
- There is a lack of systemic cytokine release in these patients, despite local inflammation.
- Findings highlight localized inflammatory processes in osteomyelitis, suggesting potential for targeted therapeutic interventions.