In vitro comparison of cytokine release from antithymocyte serum and OKT3. Inhibition with soluble and microencapsulated neutralizing antibodies.

Antilymphocyte antibodies are widely used to prevent and treat rejection after organ transplantation. Induction of cytokine release is implicated in the side effects produced by these antibodies. In this study, cytokine release induced by OKT3 was compared with antithymocyte serum (ATS) using an in vitro whole blood model. The efficacy of the microsphere form of cytokine-neutralizing antibodies to attenuate OKT3 and ATS-induced cytokine release was compared with the soluble form of cytokine-neutralizing antibodies. OKT3-induced significantly higher amounts of tumor necrosis factor-alpha and interleukin 1 beta levels compared with ATS. The microsphere form of tumor necrosis factor-alpha and interleukin 1 beta neutralizing antibodies attenuated OKT3 and ATS-induced cytokine release much more efficiently compared with the soluble form. The results suggest that the severity of the side effects is related to the amount of cytokine release. Microencapsulated cytokine-neutralizing antibodies might be a better therapeutic agent than the soluble form of cytokine-neutralizing antibodies in the treatment of side effects induced by antilymphocyte antibodies.