Effect of murine recombinant IL-2 on the course of lupus-like disease in (NZBxNZW) F1 female mice.
The exacerbation of pre-existing autoimmune diseases is a potential toxic effect of immunoactive drugs. An increase in the incidence of autoimmune thyroiditis has been noted in patients treated with human recombinant interleukin-2 (rIL-2). In contrast, human rIL-2 tends to protect mice from autoimmunity. As the effects of murine rIL-2 on autoimmunity have not been reported in mice, lupus-prone female (NZBxNZW) F1 mice were treated with 20,000 IU murine rIL-2 intraperitoneally, twice weekly for 13 weeks, beginning at 15 weeks of age. No evidence of an exacerbating effect of murine IL-2 on the lupus disease of (NZBxNZW) F1 mice was observed as no change in the following parameters were seen, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production. These results show that: 1) like human rIL-2, murine rIL-2 does not exacerbate autoimmunity in mice; 2) the biological effects of human as well as murine rIL-2 in mice differ from those seen with human rIL-2 in man. These latter findings suggest that the selection of the relevant animal species for immunotoxicity studies with recombinant cytokines and derivatives may be less straightforward than previously thought.
Ravel
G
G
MDS Pharma Services, St Germain sur l'Arbresle, France.
Christ
M
M
Ruat
C
C
Burnett
R
R
Descotes
J
J
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015551:Autoimmunity / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000633:toxicity*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000209:etiology; D011994:Recombinant Proteins / Q000633:toxicity
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007376:Interleukin-2; D011994:Recombinant Proteins; D004247:DNA