Effect of low dose recombinant interleukin 2 plus indomethacin on mortality after sepsis in a murine burn model

Abstract

Under anaesthesia, 129 8-week-old male A/J mice were subjected to a 25 per cent scald or sham burn and then resuscitated. They were divided at random into two groups. Mice from the first group were allocated into two groups. Mice from the first group were allocated into four subgroups to receive 6 days intraperitoneal (I.P.) injections as follows: (i) recombinant human interleukin 2 (rhIL-2) (250 units day-1); (ii) saline; (iii) indomethacin (5 micrograms-1 day-1); or (iv) rhIL-2 (250 units) + indomethacin (5 micrograms). Sham burned mice served as no treatment controls. All animals were subjected to peritonitis induced by caecal ligation and puncture 10 days after the burn and mortality was assessed. Mice from the second group were allocated to two subgroups to receive 6 days intraperitoneal injections of: (i) rhIL-2 + indomethacin; or (ii) saline. Animals in this group did not undergo septic challenge. They were randomly killed on days 7, 9 or 10 after the burn. Their splenocytes were harvested and assayed for response to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A), and for production of interleukin 2. Mortality rate in animals subjected to burn and septic challenge without treatment was 75 per cent; in mice receiving rhIL-2 alone it was 68 per cent, in mice receiving indomethacin alone it was 62 per cent (no significance) and in mice receiving rhIL-2 + indomethacin it was reduced to 38 per cent (P less than 0.02). Splenocytes from animals receiving combination therapy had markedly improved responses to PHA on days 7 (P = 0.01), 9 (P = 0.02), and 10 (P = 0.008), and to Con A on days 7 (P = 0.001), 9 (P = 0.002) and 10 (P = 0.001), after burn injury. Interleukin 2 production was also significantly (P = 0.004) improved by therapy with rhIL-2 + indomethacin. These data suggest that low dose rhIL-2 in combination with indomethacin may have potential use in the therapy of burn victims.