Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist

Neutralization of cytokine activity by monoclonal antibodies or receptor antagonists is beneficial in the treatment of immune and neoplastic diseases, but the necessity for continuous parenteral delivery of these anticytokine agents poses considerable practical limitations. A viable alternative is to induce a neutralizing antibody response. Using transgenic mice with high circulating levels of human interleukin-6 (hlL-6), we show that injection of the hlL-6 receptor antagonist Santi (an IL-6 variant with seven amino-acid substitutions) induces a strong anti-hlL-6 antibody response. The elicited antibodies bind circulating hlL-6 with very high affinity, totally masking it, and neutralize hlL-6 bioactivity both in vitro and in vivo