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J Rinehart, EW Delamater, L Keville and J Measel
Department of Medicine, Scott & White Clinic, Temple, TX 76508.
Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic
toxicities of antitumor chemotherapeutic agents in both mice and humans.
However, IL-1 toxicity in humans is considerable and is similar to the
systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines
with pleiotropic biologic activities, eg, fever, nausea, malaise, and
hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity
without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female,
6 weeks) were treated for 7 days subcutaneously with cortisone acetate
(CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2
micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell
counts, splenic granulocyte-macrophage colony-forming units, and spleen
cell number, and protected mice from lethal doses of carboplatin (200
mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the
day after completion of the 7 days of IL-1 administration. CA did not
significantly block the hematopoietic effects of IL-1 or the ability of
IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL- 1
administered to mice at 8 micrograms/d/mouse for 5 days induced decreased
activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic
abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5
to 2 micrograms/d) was not toxic. CA in a dose- dependent manner blocked
all of the above mentioned toxicities when administered 24 hours and 30
minutes before each IL-1 injection. CA also decreased IL-1-induced increase
in plasma tumor necrosis factor levels at the time point examined.
This article has been cited by other articles:
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
