Corticosteroid inhibition of the OKT3-induced cytokine-related syndrome--dosage and kinetics prerequisites.
The data presented extend to a larger series of 27 consecutive renal allograft recipients treated prophylactically with OKT3 our previous observation that the acute OKT3-induced clinical syndrome is related to massive release in the circulation of some cytokines, among which are tumor necrosis factor and interferon gamma. In addition, a pilot randomized study was set up including 12 consecutive patients receiving high-dose corticosteroid treatment (0.5 g solumedrol) either before or at the same time as the first OKT3 injection. Results confirm that when corticosteroids are given in sufficient amount and, importantly, 1 hr before the first OKT3 injection, they significantly decrease the release of both tumor necrosis factor and interferon gamma. In addition, the pretreatment with corticosteroids may totally abolish the IL-2 release induced by OKT3. Given the key role the massive although transient cytokine release plays in determining the OKT3-induced acute syndrome, these results provide the biological basis supporting a precise kinetics of administration of high-dose corticosteroids to better decrease the severity of the clinical reaction.
Chatenoud
L
L
INSERM U25, Hopital Necker, Paris, France.
Legendre
C
C
Ferran
C
C
Bach
J F
JF
Kreis
H
H
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D016853:Muromonab-CD3; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D007376:Interleukin-2; D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma