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.