title: Interleukin-6 treatment enhances human monocyte permissiveness for Paracoccidioides brasiliensis growth by modulating cytokine production.
abstract: The effect of interleukin (IL)-6 on cytokine production was evaluated in human monocyte cultures infected with the virulent strain of Paracoccidioides brasiliensis (Pb18). Peripheral blood monocytes from healthy individuals were preincubated for 24 h with or without human recombinant IL-6, and then challenged with Pb18 for 4 h and 18 h. P. brasiliensis growth was assessed by viable fungi recovery from co-cultures after plating on BHI-agar. Moreover, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-10 production in supernatant cultures was determined by enzyme immunoassay (ELISA). Monocyte preincubation with IL-6, and challenged with Pb18 for 4 h, led to significantly higher fungi recovery compared to non-treated co-cultures. The pretreatment of monocytes with IL-6 induced an inhibitory effect on TNF-alpha and IL-10 production during 18 h fungal infection. Otherwise, an autocrine stimulatory effect on IL-6 production was detected at 4 h and 18 h as represented by an elevation in IL-6 levels. The reduction in TNF-alpha levels and stimulation of IL-6 production induced by previous IL-6 treatment might be responsible for a significant increase in fungal growth in human monocytes. The results suggest that IL-6, by exerting a modulatory effect on cytokines production, makes monocyte more permissive for fungal growth.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
authors.forename: Keila Zaniboni
authors.initials: KZ
authors.lastname: Siqueira
authors.forename: Angela Maria Victoriano De
authors.initials: AM
authors.lastname: Campos Soares
authors.forename: Luciane Alarcão
authors.initials: LA
authors.lastname: Dias-Melicio
authors.forename: Sueli Aparecida
authors.initials: SA
authors.lastname: Calvi
authors.forename: Maria Terezinha Serrão
authors.initials: MT
authors.lastname: Peraçoli
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D050296:Microbial Viability; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D010228:Paracoccidioides / Q000254:growth & development* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10