Combination immunotherapy and antifungal chemotherapy.
Historical clinical observations suggested that cellular immunity is central in the outcome of deep fungal infections, and experimental observations later proved this. Unstimulated effector cells interact synergistically with antifungal drugs. Recombinant cytokines, of which interferon gamma (IFN-gamma) is the most prominent, stimulate several host-effector cells (macrophages, monocytes, neutrophils) for antifungal activity. Effector cells stimulated by such molecules (data with macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor with azoles are presented as examples) also have enhanced synergistic activity with antifungals. A tilt toward a type 1 T-helper (Th1) cell pathway seems essential in antifungal host defenses. Cytokines (and anticytokines) that promote this pathway can be protective in vivo and act cooperatively with antifungal drugs. Observations with interleukin (IL)-12, IFN-gamma, and anti-IL4 illustrate this. The clinical applications of these strategies are just beginning.
Stevens
D A
DA
Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, California 95128-2699, USA.
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use; D015847:Interleukin-4 / Q000008:administration & dosage / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy* / Q000276:immunology; D018417:Th1 Cells; D018418:Th2 Cells
D000935:Antifungal Agents; D016207:Cytokines; D015847:Interleukin-4; D000666:Amphotericin B; D007371:Interferon-gamma