title: Regulatory effect of interleukin-4 in the innate inflammatory response to Rhodococcus aurantiacus infection in mice.
abstract: Interleukin (IL)-4 promotes the regression of granulomas during the late phase of Rhodococcus aurantiacus infection. In this study, the contribution of IL-4 to the initial response against this bacterium was investigated using IL-4-deficient mice. Compared with wild-type (WT) mice, IL-4-deficient mice displayed remarkably lower tumor necrosis factor (TNF)-α and IL-6 secretion in the liver, spleen, and blood at the initial phase of infection, along with improved survival. IL-4-deficient mice also showed diminished IL-10 secretion in the spleen and blood; however, hepatic IL-10 levels were similar to those observed in WT animals, and were concomitant with augmented interferon (IFN)-γ production and decreased bacterial burden in the liver at the early infection phase. Histological examination revealed reduced hepatic granuloma formation in infected IL-4-deficient mice. On challenge with heat-killed R. aurantiacus, IL-4-deficient mouse macrophages showed reduced expression of TNF-α, IL-6, and IL-10 at both the gene and protein levels compared with WT mouse cells. These findings indicate that during the initiation of R. aurantiacus-induced inflammation, IL-4 deficiency attenuates cytokine responses in macrophages, which contributes to amelioration in mouse survival and reduction of granulomatous inflammation, and augments a hepatic IFN-γ response which transiently accelerates bacterial elimination.
authors.affiliation: 1 Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University , Sapporo, Japan .
authors.lastname: Yimin
authors.forename: Masashi
authors.initials: M
authors.lastname: Kohanawa
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000193:Actinomycetales Infections / Q000276:immunology* / Q000628:therapy; D000818:Animals; D058491:Bacterial Load; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012240:Rhodococcus / Q000276:immunology*; D012507:Sarcoidosis / Q000276:immunology* / Q000628:therapy
chemical_list: D015847:Interleukin-4