Administration in vivo of recombinant interleukin 2 protects mice against septic death.
Administration in vivo of recombinant interleukin 2 (rIL-2) to mice induces a polyclonal IgM response. When co-administered with a specific antigen, rIL-2 can enhance concentrations of murine IgM antibodies specific for the antigen by fivefold within 7 d of initial treatment. IgM antibodies that are induced after injection of rIL-2 include antibodies specific for J5, a cell wall core lipopolysaccharide (LPS) antigen that is shared by the different members of the Enterobactericeae family. We report here that mice pretreated with rIL-2 or immunized with J5 antigen 7 d before bacterial challenge were protected from septic death that is caused by intraperitoneal challenges with Escherichia coli. Optimal protection was provided by a combined J5 antigen and rIL-2 treatment. Acquisition of the rIL-2 and J5 antigen-induced protection against lethal bacterial infection coincided temporally with maximal serum IgM titers that also contained IgM antibodies specific for the J5 antigen. In passive immunization experiments, the affinity-purified IgM fraction in sera of rIL-2-treated animals was identified as necessary and sufficient for protection. The IgM-depleted serum had no protective effect. The nonspecific augmentation of host-defense mechanisms without the induction of endotoxin manifestations makes rIL-2 a potential candidate to any alternative LPS-containing vaccines for the prevention of bacterial infections by gram-negative organisms since the core LPS antigen is shared among gram-negative bacteria.
Weyand
C
C
Goronzy
J
J
Fathman
C G
CG
O'Hanley
P
P
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000150:complications; D005260:Female; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000150:complications; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007075:Immunoglobulin M; D007376:Interleukin-2; D008070:Lipopolysaccharides; D011994:Recombinant Proteins