John H.Rex, MD


Recent work has increasingly demonstrated the important role of all levels of the immune defense system against Candid, Aspergillus, and the other moulds that cause fungal infections in severly ill patients in the critical care and cancer settings.PMNL: The importance of the polymorphonuclear leukocyte (PMNL) is incontrovertible and this cell is generally assumed to have the most significant direct action The ability of PMNL to directly kill Candida and Aspergillus is obvious as are the clinical implications of PNNL deficiency. However, recent work has also show that not all PMNL are equal: PMNL from some patient groups (e.g., neonates, patients with AIDS) can have significant functional deficiencies that appear in part to be due to cytokine deficiencies and correctable with cytokine supplementation.Macrophages: Depletion enhances susceptibility to invasive candidiasis and functional deficiencies of NO production also enhance susceptibility in murine systems. They can also directly kill Aspergillus conidia and produce pro-inflammatory cytokines in response to fungi.Lymphocytes (Direct): While usually thought of in terms of their cytokine response, recent work has shown a direct ability of lymphocytes to inhibit growth of C. neoformans (seen with CD4+, CD8+, and NK cells) and Candida (seen with CD8+ cells). In addition IL-2 activated T lymphocytes can alter cell wall morphology and interfere with adherence of Aspergillus without affecting viability.Lymphocytes (Indirect): Substantial work has now correlated a Th1 profile lymphocyte response- with resistance to invasive candidiasis and a Th2 response with increased susceptibility. Similar, preliminary data exist for C. neoformans. Some, but not a1l healthy donors respond to Aspergillus antigens with a Th1-profile response and allergic bronchopulmonary aspergillosis is associated with a Th2 profile response. B cells/Antibodies: These have long been ignored for fungal infectious but recent data have strongly supported the notion of a protective role for at least some antibodies in crytpococcal meningitis as well as in local immunity to mucosal candidiasis.Clinical Implications: The observations that can be most immediately translated into clinical tools for treatment of invasive candidiasis and aspergillosis are those that focus on modulation of phagocyte function by cytokines. In particular, the ability to modulate PMNL function and number with cytokines that are both readily available and well tolerated provide exciting new therapeutic modalities that may benefit selected patients.

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13th Congress of the International Society for Human and Animal Mycology
    • ISHAM 13th (1997)