Gene exchange of thyA for interleukin-10 secures live GMO bacterial therapeutics.

Extract: The exponential outburst of knowledge in molecular immunology has provided us with an in depth insight into the biological activity of cytokines. These are small, freely diffusible proteins that, together with numerous growth factors and chemokines, act as messengers by which cells of the immune system communicate with each other and with most other tissues in the body. As such, these molecules are able to regulate many aspects of the immune response in which numerous cells and tissues may be involved at any one time. Most often, cytokines are active in extremely low concentrations. It is for these reasons that they are considered a tempting source of candidate therapeutics for the treatment of immune disorders or of value for boosting prophylactic immune therapies. The field has, however, seen major technical obstacles to the proficient use of many cytokines. Interleukin-10 (IL-10), an anti-inflammatory cytokine, can certainly serve as one of the most prominent examples of this striking combination of high promises -- for targeting immune diseases such as Crohn's disease and asthma -- being blocked in its application by equally high complications such as unacceptable side effects and high clearance. As many of the problems arise from the systemic distribution of IL-10 in the body, targeted delivery could enable the successful use of recombinant IL-10. Here again, however, technical hurdles such as the inherent acid sensitivity of IL-10 alongside the intrinsic high cost of any purified recombinant cytokine probably underlie the non-existence of readily available classical formulations for mucosal application of this cytokine.