In vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis.
Polymorphonuclear neutrophils are critical for resolution of bacterial infections. In tissues, most of the neutrophils quickly die through apoptosis. Using propidium iodide DNA staining and DNA gel electrophoresis, we found that spontaneous apoptosis of neutrophils from patients suffering osteomyelitis (n = 52) was significantly decreased in relation to control neutrophils (n = 20) (40.2% +/- 25.2% versus 54.5% +/- 23.5%; P < 0.03). Incubation of neutrophils from normal volunteers with sera from patients with osteomyelitis reduced apoptosis from 79.1% +/- 14.8% in control sera to 62.2% +/- 18.7% in osteomyelitis sera. A significant increase of serum interleukin-6 (IL-6) and IL-1alpha was found in osteomyelitis (IL-6, 8.8 +/- 11.9 pg/ml versus 1.8 +/- 1.2 pg/ml in controls [P < 0.004]; IL-1alpha, 3.8 +/- 6.4 pg/ml versus 1.0 +/- 2.2 pg/ml in controls [P < 0.02]). No differences in the levels of other cytokines, such as tumor necrosis factor alpha, were found. There was an inverse correlation between IL-6 levels and neutrophil apoptosis (r = -0.855; P < 0.007), but this was not the case for other cytokines. The antiapoptotic effect of the osteomyelitis sera was reversed with anti-IL-6 antibodies (P < 0.03) and was reproduced with recombinant human IL-6 (P < 0.001). The longer life span of neutrophils in osteomyelitis induced by IL-6 could contribute to the tissue damage that occurs in these chronic bone infections.
Asensi
Víctor
V
Infectious Diseases Unit, Hospital Central de Asturias, Oviedo University Medical School, C/Celestino Villamil s/n, 33006 Oviedo, Spain. vasensia@medynet.com
Valle
Eulalia
E
Meana
Alvaro
A
Fierer
Joshua
J
Celada
Antonio
A
Alvarez
Victoria
V
Paz
José
J
Coto
Eliecer
E
Carton
José Antonio
JA
Maradona
José Antonio
JA
Dieguez
Angeles
A
Sarasúa
Julián
J
Ocaña
Marcos G
MG
Arribas
José Manuel
JM
D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010019:Osteomyelitis / Q000378:metabolism*; D044967:Serum / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6