IL-10 EXERTS SUPPRESSIVE AND ENHANCING EFFECTS ON ANTIFUNGAL ACTIVITYOF MONONUCLEAR PHAGOCYTES AGAINST ASPERGILLUS-FUMIGATUS

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 approximate ly 40% suppression of superoxide anion (O-2(-)) production in response to PMA and FMLP (p less than or equal to 0.003), and anti-IL-10 conta ining supernatant neutralized the IL-10 effect, IL-10 (20 ng/ml)-pretr eated MNCs exhibited decreased damage of Aspergillus hyphae after 2 to 4 days (55-98% decrease, p less than or equal to 0.04). The MNC phago cytic 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), res pectively. MNC capacity to inhibit intracellular germination was margi nally enhanced (p=0.04) and intracellular conidiocidal activity was un affected 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-macrop hage CSF (20 ng/ml), but not macrophage CSF (15 ng/ml), appeared to co unteract suppressive IL-10 effects, Thus, IL-10 suppresses oxidative b urst and antifungal activity of MNCs against Aspergillus hyphae, while increasing their phagocytic activity, These findings further elucidat e a potential role of IL-10 in the pathogenesis of invasive aspergillo sis, which may lead to new treatment strategies.