Despite the great efforts put into their development, the list of clinically approved
immunological adjuvants is still very short. Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required. Derivatives of
muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall
peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects.
Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2. The transcriptional response of
murabutide-stimulated macrophages revealed enhanced expression of genes coding for various
proteins such as immune mediators and their receptors,
transcription factors and
kinases,
ion channels/transporters and
proteins involved in cell metabolic activity, thus reflecting a broad spectrum of
biological effects. In addition to its well recognized adjuvant effect,
murabutide has also been shown to enhance the host's resistance against microbial
infections, nonspecific resistance against
tumors and the induction of
cytokines and
chemokines implicated in enhancing the immune response and hematopoesis. This article provides an insight into the mechanism of action of
murabutide and its interactions with the cells of the immune system in vitro and in vivo. On account of its numerous
biological effects,
murabutide has been the subject of several clinical studies. Many of these have confirmed its potential to synergize with
cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic
viral diseases, as well as reducing the
cytokine dosage needed to achieve a
therapeutic effect. This review covers the findings of all relevant studies and focuses on the role of
murabutide and its potential in the treatment of several microbial diseases.