REDUCTION OF MORBIDITY AND CYTOKINE RELEASE IN ANTI-CD3 MOAB-TREATED MICE BY CORTICOSTEROIDS

被引:72
作者
FERRAN, C
DY, M
MERITE, S
SHEEHAN, K
SCHREIBER, R
LEBOULENGER, F
LANDAIS, P
BLUESTONE, J
BACH, JF
CHATENOUD, L
机构
[1] HOP NECKER ENFANTS MALAD, INSERM, U25, CNRS, UA 122, 161 RUE SEVRES, F-75730 PARIS 15, FRANCE
[2] FAC SCI & TECH MT ST AIGNAN, RECH ENDOCRINOL MOLEC GRP, CNRS, UA 650, F-76130 Mont St Aignan, FRANCE
[3] WASHINGTON UNIV, SCH MED, DEPT PATHOL, ST LOUIS, MO 63110 USA
[4] UNIV CHICAGO, BEN MAY INST, CHICAGO, IL 60637 USA
[5] HOP NECKER ENFANTS MALAD, BIOSTAT & INFORMAT MED LAB, F-75730 PARIS 15, FRANCE
关键词
D O I
10.1097/00007890-199010000-00023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In keeping with the in vitro mitogenic properties of anti-CD3 MoAbs, the first injections of anti-CD3 are invariably responsible for an in vivo cellular activation. This activation induces a massive cytokine release in the circulation (TNF, IFNγ, IL-2, IL-6, and IL-3). Paralleling this release, a severe clinical reaction occurs in OKT3-treated patients and in 145 2C11- treated mice. Corticosteroids both in vitro and in vivo inhibit the production of several cytokines involved in the anti- CD3 reaction. A single 1 mg hydrocortisone dose was administered to 145 2C11- treated mice according to different kinetics schedules. When given 1 hr prior to the anti-CD3 MoAb, hydrocortisone exerted a beneficial effect on the mouse physical reaction. Hypothermia was totally abrogated at the 4-hr time point. Diarrhea decreased by 50%. Hypomotility improved although not significantly. This improvement correlated with a major modification in the anti-CD3 pattern of cytokine release. At the 90-min blood withdrawal time point cytokine serum levels showed a 100% decrease for IFNγ, an 88% decrease for IL-6, an 85% decrease for IL-2, and a 75% decrease for TNF. At 4 hr IL-2 serum levels were diminished by 65%; IL-6, IL-3, and IFNγ serum levels were comparable to controls; and, interestingly, TNF was still detected, whereas it has already disappeared when 145 2C11 was administered alone. Importantly, when given more than 1 hr prior to anti-CD3 injection, corticosteroids were ineffective. To conclude, high doses of corticosteroids must be given with a precise kinetics-i.e. 1 hr prior to anti-CD3 MoAb-to achieve their maximal beneficial effect in the prevention of the anti- CD3 reaction. © 1990 by Williams & Wilkins.
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页码:642 / 648
页数:7
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