Immunotherapy for invasive fungal infections: from bench to bedside

Immunotherapy for invasive fungal infections has been an area of significant research and clinical interest since the first-half of the twentieth century when hyperimmune equine immunoglobulin was first successfully administered to patients with acute and chronic cryptococcal meningitis. Since that time, effective antifungal compounds have been developed, but a much more complex array of host disorders have also emerged creating an even greater need for immunotherapy in conjunction with conventional antifungal therapy. In this review, the scientific foundation supporting the use of various immunotherapeutic interventions including granulocyte infusions, cytokine growth factors, pro-inflammatory cytokines including IFN-gamma and interleukin-12, immunoglobulin therapy, and active immunization will be discussed. Clinical data supporting the use of these interventions are often scant and inconclusive, however, relevant clinical information will be presented. In theory, adjunctive immunotherapy for invasive fungal infections has significant potential for improving clinical outcomes in a growing population of patients at risk for these potentially devastating infections. Clearly, randomized double-blind clinical trials will need to be performed to better understand the precise role of these interventions. There are several obstacles preventing the conduct of these studies, but these pressing clinical issues must be addressed through carefully considered study design and effective implementation.