Prophylactic administration of interleukin-2 protects mice from lethal challenge with gram-negative bacteria.

Abstract

Prophylactic administration of recombinant human interleukin-2 (IL-2) in mice enhanced survival and produced complete recovery from an otherwise lethal acute bacterial infection. IL-2 was administered as a single intraperitoneal or intravenous bolus dose to CDI mice 18 h before challenge with a lethal dose of a clinical isolate of Escherichia coli type O2 (minimal 100% lethal dose, 6 X 10(7) CFU per mouse). At IL-2 dosages of 7 X 10(6) U/kg, 90% of treated CDI mice survived as compared to 0% for the excipient buffer control animals (P less than 0.001). This protective effect was also demonstrable in immune-deficient beige mice. The IL-2 effect was dose dependent; protection was consistently observed in mice pretreated with IL-2 at doses ranging from 1.8 X 10(6) to 7 X 10(6) U/kg. However, at 3.5 X 10(5) U/kg the protective effect was more variable. The route of administration of IL-2 was shown to play an important role; when IL-2 and challenge bacteria were given by the same route (either intravenously or intraperitoneally), protection was readily observable, but when IL-2 and challenge bacteria were given by different routes, little or no protective effect was observed. The protective effect was fully inducible as early as 1 h after IL-2 administration and was effective against various strains of gram-negative bacteria, indicating that the probable mode of action represents control of the establishment of infection by increased activity of the nonspecific host defense mechanisms. The IL-2 effect was abrogated by the administration of carrageenan, suggesting a possible role of macrophages. These data demonstrate that IL-2 may be a potentially useful adjunct for the prophylaxis of bacterial infections in both clinical and veterinary medicine.

• Authors: K T Chong
• Journal: Infection and immunity (Infect Immun) Vol. 55 Issue 3 Pg. 668-73 (Mar 1987) ISSN: 0019-9567 [Print] United States
• PMID: 3546134 (Publication Type: Journal Article)

Chemical References

• Interleukin-2

Topics

• Animals
• Escherichia coli Infections (complications, immunology, prevention & control)
• Female
• Immunity, Cellular (drug effects)
• Immunologic Deficiency Syndromes (complications, drug therapy, immunology)
• Interleukin-2 (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains (immunology)