Systemic bacteraemia following haemorrhagic shock in mice: alleviation with oral interleukin 6

Abstract

A murine model of haemorrhagic shock was used to investigate bacterial translocation from the gut and subsequent systemic immunoreduction. Anaesthetized mice were bled from the femoral artery, and held at a mean arterial blood pressure of 35 mm Hg for one hour then resuscitated with shed blood and two-fold volume lactated Ringer's solution. Upon awakening, they were given cytokines or control media orally. Bacteriological cultures of livers, spleens and mesenteric lymph nodes from haemorrhaged mice given cytokine had significantly fewer bacteria/gm of tissue than those given media. Recombinant IL-6 mimicked the effects seen with crude cytokines. Reduction of proliferation among spleen cells from haemorrhaged mice was observed and could be partially returned to normal by cytokine feeding. Mixing experiments in which cells from haemorrhaged mice were added to those of normal mice in an MLR showed no suppressor activity. Flow cytometry analysis revealed a reduction in CD 3+ cells at 16 hours post-haemorrhage in mice fed control media or cytokines, suggesting that reduced proliferative capacity may be due to loss of function rather than active suppression. Histological examination of the intestines of haemorrhaged mice fed cytokines or media revealed restoration of intestinal mucosal integrity by cytokine administration. These results suggest that oral administration of IL-6 may be an important treatment for the prevention of systemic sepsis following haemorrhage.