HIGH-DOSE INTERLEUKIN-2 PROMOTES BACTERIAL TRANSLOCATION FROM THE GUT

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) t herapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be importan t. Fifty-one male rats were randomised to receive rIL-2 by intraperito neal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) ( n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, heal histomorphology was assessed and the mesenteric lymph no de complex cultured. Results showed that colonisation of mesenteric ly mph nodes with Escherichia coil occurred in all rats treated with 10(5 ) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics acid occasional mucosal disruption w as seen only in the group receiving 10(5) IU. These data show that rIL -2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.