Cytokines and fungal infections

Abstract

Summary The very poor outcome of invasive fungal infections (IFI) in patients with haematological malignancies or recipients of haematopoietic stem cell transplantation is largely attributed to their compromised host defence mechanisms. The restoration or augmentation of immune responses in these patients is now considered as one of the cornerstones of effective antifungal therapy. Major advances in the field of experimental immunology have provided insight on the important regulatory role of cytokines in both innate and adaptive immunity to fungal pathogens. Preclinical studies have convincingly demonstrated that immunomodulation with cytokines can enhance the antifungal activity of neutrophils and monocytes/macrophages as well as upregulate protective T‐helper type 1 adaptive immune responses. Evidence on the clinical use of cytokines in immunocompromised hosts with IFI is, however, still scant and inconclusive. The present review summarizes experimental and clinical data on the role of cytokines in the immune response to fungal pathogens and on their potential use for prevention or treatment of fungal infections. Implications for future research are also briefly discussed.

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…Cytokines are known to play a major role in a variety of immunological, inflammatory and infectious diseases [128]. In general, a clinical classification divides immunological cytokines into those that promote proliferation and functioning of type-1 helper T-cells (Th1 cells), e.g.…”

Mucormycosis (Zygomycosis)

“…In support of these general recommendations for cytokine augmentation of host defense are recent in vitro studies demonstrating enhancement of neutrophil activity against R. oryzae and other species of Mucorales in the presence of interferon-γ and GM-CSF [31]. An alternative approach has been the administration of granulocyte transfusions in neutropenic patients with invasive fungal infections [29,30]. These immunomodulatory interventions may be considered on an individual patient basis as adjunctive therapy for mucormycosis in immunocompromised hosts.…”

“…These immunomodulatory interventions may be considered on an individual patient basis as adjunctive therapy for mucormycosis in immunocompromised hosts. Nonetheless, as a caveat, there is a lack of adequately powered clinical trials to evaluate their clinical efficacy and potential complications [6,29,30].…”

“…However, even with these measures, spontaneous restoration of phagocytic activity or recovery from neutropenia is likely to occur after several days, during which time the infection may progress. In vitro and in vivo studies, as well as case reports, have suggested that the administration of cytokines, such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ, may accelerate immune recovery [30]. In support of these general recommendations for cytokine augmentation of host defense are recent in vitro studies demonstrating enhancement of neutrophil activity against R. oryzae and other species of Mucorales in the presence of interferon-γ and GM-CSF [31].…”

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

“…In addition, immunomodulators can play a role in the regulation of pathogen-induced immunopathology. For instance, a Th1-biased immune response is required for the protection against fungal infections [86,97]. Immunocompromised patients lack the ability to mount appropriate immune responses against most pathogens.…”