High-dose interleukin 2 promotes bacterial translocation from the gut.
Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal 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, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli 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 and occasional mucosal disruption was 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.
Reynolds
J V
JV
Department of Surgery, St. James University Hospital, Leeds, UK.
Murchan
P
P
Leonard
N
N
Gough
D B
DB
Clarke
P
P
Keane
F B
FB
Tanner
W A
WA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004064:Digestive System / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D007376:Interleukin-2 / Q000633:toxicity*; D008198:Lymph Nodes / Q000382:microbiology*; D008297:Male; D008643:Mesentery; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity
D007376:Interleukin-2; D011994:Recombinant Proteins