title: IL-10 exerts suppressive and enhancing effects on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus.
abstract: Invasive aspergillosis has emerged as a frequent and serious infection in immunocompromised patients. We studied the effects of human IL-10 on antifungal activity of monocytes (MNCs) from healthy adults against Aspergillus fumigatus after incubation with IL-10 at 37 degrees C for 2 to 4 days. IL-10 (2-20 ng/ml)-pretreated MNCs exhibited approximately 40% suppression of superoxide anion (02-) production in response to PMA and FMLP (p < or = 0.003), and anti-IL-10 containing supernatant neutralized the IL-10 effect. IL-10 (20 ng/ml)-pretreated MNCs exhibited decreased damage of Aspergillus hyphae after 2 to 4 days (55-98% decrease, p < or = 0.04). The MNC phagocytic activity against conidia, as assessed by microscopy (percentage of phagocytosing MNCs and number of intracellular conidia per MNC) as well as by colony counting (colonies grown from intracellular conidia), was enhanced by 127% (p = 0.006), 14% (p = 0.03), and 23% (p = 0.009), respectively. MNC capacity to inhibit intracellular germination was marginally enhanced (p = 0.04) and intracellular conidiocidal activity was unaffected by IL-10. IL-4 (5 ng/ml) did not change the up-regulatory IL-10 effect on phagocytosis. IFN-gamma (25 ng/ml) and granulocyte-macrophage CSF (20 ng/ml), but not macrophage CSF (15 ng/ml), appeared to counteract suppressive IL-10 effects. Thus, IL-10 suppresses oxidative burst and antifungal activity of MNCs against Aspergillus hyphae, while increasing their phagocytic activity. These findings further elucidate a potential role of IL-10 in the pathogenesis of invasive aspergillosis, which may lead to new treatment strategies.
authors.affiliation: Third Department of Pediatrics, University of Thessaloniki, Hippokration Hospital, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Roilides
authors.forename: A
authors.initials: A
authors.lastname: Dimitriadou
authors.forename: I
authors.initials: I
authors.lastname: Kadiltsoglou
authors.forename: T
authors.initials: T
authors.lastname: Sein
authors.forename: J
authors.initials: J
authors.lastname: Karpouzas
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000032:analysis
chemical_list: D000276:Adjuvants, Immunologic; D000935:Antifungal Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D013481:Superoxides; D016753:Interleukin-10