Title:Murabutide Revisited: A Review of its Pleiotropic Biological Effects
Volume: 20
Issue: 16
Author(s): Ziga Jakopin
Affiliation:
Keywords:
Murabutide, immunomodulator, immunostimulant, immunoadjuvant, vaccine, HIV–1, HCV, leprosy
Abstract: 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.
