Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice.
Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.
Gough
D B
DB
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Moss
N M
NM
Jordan
A
A
Grbic
J T
JT
Rodrick
M L
ML
Mannick
J A
JA
D000818:Animals; D002056:Burns / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010538:Peritonitis / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007376:Interleukin-2; D011994:Recombinant Proteins