Immunomodulator Tuftsin Augments Anti-fungal Activity of Amphotericin B Against Experimental Murine Candidiasis

Abstract

In the present study, we report the potential of an immunomodulator tuftsin in increasing the efficacy of liposomised Amphotericin B (Amp B) against drug sensitive as well as drug resistant experimental murine candidiasis. The Amp B containing liposomes demonstrated strong potential of eliminating systemic candidiasis (70% survival) in animals infected with Amp B sensitive strain of Candida albicans (C. albicans). The same liposomal formulation was found to be ineffective in treatment of animals infected with drug resistant C. albicans. However, the co-administration of liposomal formulation of Amp B along with an immunomodulator tuftsin, was found to be competent enough in curing even the drug resistant candidiasis. In contrast, none of the animals survived in the control groups, which were treated with free or liposomised Amp B (without tuftsin). Further, the effect of liposomised tuftsin, on T-cell proliferation as well as antibody production reveals that tuftsin elicits strong immunopotentiating effects as well. The pretreatment with liposomised tuftsin prior to challenging the animals with drug resistant C. albicans infection has also been effective and shows an extra edge in prophylactic perspectives.

Co-administration of immunomodulator tuftsin and liposomised nystatin can combat less susceptibleCandida albicansinfection in temporarily neutropenic mice

“…The immuno-potential activity of tuftsin was further supported by its significant increase in ovalbumin specific T-cell proliferation by animals immunised with OVA-bearing-tuftsin liposomes [15]. In this study, we confirm its prophylactic action against candidiasis by pretreating the animals with liposomised-tuftsin prior to C. albicans infection.…”

“…In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to consider that host factors such as degree of immunological weakness, recovery of immune functions to normality, may contribute significantly in successful pathogen elimination [17,18]. In previous studies, we demonstrated that the use of tuftsin bearing Amp B and nystatin liposomes leads to the successful treatment of C. albicans infection in Balb/c mice [15,28]. It seems that concomitant delivery of the antimicrobial agents and immunomodulators to the pathogen‐harbouring host not only facilitates in targeted delivery of the drug but also activates the immune system leading to a complete elimination of the deep‐seated fungal infections [15,18].…”

“…Different vital organs, i.e. liver, lung, kidney and spleen were analysed for their fungal burden as described earlier [15]. Briefly, weighed portions of the given organ were homogenised in 5 ml of sterile normal saline solution and different dilutions of the suspension were plated on SD agar plates containing chloramphenicol and gentamicin.…”

“…In addition, tuftsin elicits a chemotactic, migration‐enhancing and mitogenic response in leukocytes [12]. In fact, the immunomodulator properties of tuftsin make it an extremely attractive agent in the therapy of fungal as well as other infectious diseases [13–16].…”

Immunomodulatory properties of new conjugates of muramyl dipeptide and nor-muramyl dipeptide with retro-tuftsin (Arg-Pro-Lys-Thr-OMe)

“…Tuftsin has been also reported to combat not only bacterial infections. A few groups of scientists have proved that co-administration of tuftsin and antibiotics leads to successful treatment of opportunistic infection diseases such as: candidiasis [19][20][21][22][23], aspergillosis [24,25], brugian filariasis [26] and leishmania infection [27]. In spite of its pleiotropic activity, tuftsin is not an efficient therapeutic agent, due to high susceptibility to biodegradation [9].…”