OKT3 first-dose reaction: association with T cell subsets and cytokine release

Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release. Twenty-three kidney or kidney/pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score less than or equal to 3); Group 2 patients (N = 12) had more severe reactions (score greater than or equal to 5). All patients demonstrated a significant rise in serum TNF alpha from baseline to two hours after OKT3 (9 +/- 3 pg/ml to 378 +/- 54 pg/ml, P less than 0.0001), and there was significant correlation between reaction scores and two-hour TNF alpha levels (P = 0.005). Group 2 patients had higher TNF alpha levels at two hours than did Group 1 patients (484 +/- 75 pg/ml vs. 263 +/- 62 pg/ml, P = 0.04). Levels of IL2 and IFN gamma were not elevated at any sampling time.(ABSTRACT TRUNCATED AT 250 WORDS)