Cytokines as therapy for opportunistic fungal infections

• Published in: Research in immunology (Paris) 1998-05, Vol.149 (4), p.478-488
• Main Authors: Kullberg, B.J., Anaissie, E.J.
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - therapeutic use; Humans; Immunotherapy; Leukocyte Transfusion; Mycoses - prevention & control; Mycoses - therapy; Opportunistic Infections - prevention & control; Opportunistic Infections - therapy
• ISSN: 0923-2494
• DOI: 10.1016/S0923-2494(98)80771-2

Recently, great progress has been made in the development of antifungal therapy. New classes of antifungal drugs have been introduced, that bear promise for achieving cure from infection and a lower incidence of adverse effects. Despite these developments, treatment failure is still a significant problem, amounting to 20-30% of patients with the most common opportunistic fungal infections. In specific groups of patients, such as those with persistent neutropenia, failure rates are even substantially higher. Resolution of these infections is often dependent on recovery from granulocytopenia or restoration of cellular immunity, indicating that host defence mechanisms are extremely important in the clearance of these pathogens. Therefore, immunotherapy aimed at enhancing host defence mechanisms may prove extremely productive in this field. Such interventions may be targeted at increasing the numbers of phagocytic cells, modulating the kinetics of these cells at the site of infection or activating phagocytes to kill the pathogenic fungal organisms more effectively. These effects of professional phagocytes are controlled by the differentiation of T helper cell subsets, and this Th1/Th2 balance itself may be the target of immunotherapy as well. For many decades, investigators have attempted to enhance the non-specific resistance to fungal infection by injection of microorganisms, such as Mycobacterium bovis BCG or Candida albicans, or microbial cell wall constituents, such as bacterial endotoxin or muramyl dipeptides. Most of these compounds are known to stimulate the synthesis of proinflammatory cytokines interleukin-1 (IL1), interferon- gamma (IFN gamma ) or tumour necrosis factor- alpha (TNF alpha ). The immunomodulatory effects of such agents are at least partly mediated by the induction of these cytokines. The recent availability of a wide range of recombinant cytokines and haematopoietic growth factors has now opened the door to the application of immunotherapy in invasive fungal infections.