Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis

Gabriella Freitas Ferreira,Olindo Assis Martins-Filho,Luiz Simeão Do Carmo,Lucia Alves De Oliveira Fraga,Cícero Moraes,Elizabeth Castro Moreno,Rodrigo Correa-Oliveira,Alda Maria Soares Da Silveira,Andréa Teixeira-Carvalho,Luiz Cosme Cotta Malaquias

doi:10.1590/s0074-02762012000300009

Abstract

We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.

Highlights

Osteomyelitis is a bone disease characterised by progressive inflammatory destruction of the infected bone and recruitment of osteocytes to the site of infection
Staphylococcus aureus is the microorganism most frequently isolated from posttraumatic and haematogenous osteomyelitis (Lew & Waldvogel 1997, Jorge et al 2010). The virulence of this bacterium is associated with its ability to penetrate the bone tissue, evade the host defences and secrete exotoxins, such as the superantigen staphylococcal enterotoxin A (SEA) (Nair et al 2000), which 57% of S. aureus strains isolated from chronic osteomyelitis patients (OST) are able to produce (Sourek et al 1979)
Because the cellular immune response during chronic staphylococcal osteomyelitis has not been fully characterised in humans, we investigated the contribution of antigen-induced cellular reactivity, cytokine production in peripheral blood mononuclear cells (PBMCs) and serum nitric oxide (NO) levels to disease pathogenesis in chronic staphylococcal OST patients

Summary

Introduction

Osteomyelitis is a bone disease characterised by progressive inflammatory destruction of the infected bone and recruitment of osteocytes to the site of infection. Because the cellular immune response during chronic staphylococcal osteomyelitis has not been fully characterised in humans, we investigated the contribution of antigen-induced cellular reactivity, cytokine production in peripheral blood mononuclear cells (PBMCs) and serum NO levels to disease pathogenesis in chronic staphylococcal OST patients.

Results

Conclusion