Immunomodulating Activity of Antifungal Drugs

Abstract

1. The immunomodulating activity of antifungal drugs was reviewed. Although results are conflicting, all azole drugs tend to be immunosuppressive, except for fluconazole, which has no immunologic effect. In contrast, the polyene antibiotic amphotericin B (AMPH) is immunostimulatory. 2. AMPH induced host resistance to Pseudomonas aeruginosa infection in mice, whereas no azole drugs did so. 3. Polymorphonuclear leukocytes are activated by AMPH, but not by any azole drugs, in terms of the level of their adherence. 4. No azole drugs induce in vitro tumor necrosis factor alpha (TNF) production by macrophages, whereas AMPH slightly but substantially does so. 5. AMPH potently primes macrophages in vitro and in vivo so that they produce large amounts of TNF after the secondary stimulation (triggering) by bacterial lipopolysaccharides or a streptococcal preparation used for antitumor immunotherapy, OK432. 6. Viable or heat-killed Candida albicans cells are capable of inducing in vitro TNF production by macrophages. This activity of the fungal cells is enhanced by AMPH.

Immunomodulatory activity of itraconazole in lung

“…This triazole scaffold is extremely versatile and has a broad spectrum of pharmacological activities [15]. Recently, there has been interest in the non-antifungal effects of this group of drugs, because knowledge of these properties could enhance both their clinical usefulness and therapeutic efficacy [3].…”

“…Although several papers have described the in vitro effects of some antifungals on the activities of macrophages, monocytes, and neutrophils from animals and humans [2,3,7,8], little is known about the in vivo effects of antifungal drugs.…”

“…The marked increase in the incidence of fungal infections in recent decades, principally due to the growing number of patients with AIDS and organ transplants, has awakened interest not only in developing new antifungal drugs but also in evaluating the effects that current antifungals have on the host immune response [1][2][3]. It is important to ensure that these agents per se do not exert negative effects on the host immune system.…”

Augmentation of production of TNF-alpha and anti-tumour activity by an amphotericin B preparation for clinical use in mice

“…To check that it was amphotericin B that augmented the induction of endogenous TNF, we examined the effect of these components on the induction. As shown in Figure 4A Yamaguchi et al, 1993 . We have confmned that neither FK23 nor amphotericin B has any significant anti-tumour activity in this Meth A model.…”

“…Efficient induction of TNF reportedly requires two steps of macrophage stimulation -a priming step and a triggering step (Mizuno, 1992). We recently demonstrated the priming activity of amphotericin B to induce in vitro and in vivo TNF production in mice Yamaguchi et al, 1993). This suggests that amphotericin B may elicit some anti-tumour activity in vivo when used in combination with an appropriate triggering agent for TNF production.…”