Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice.
The interaction between interleukin-10 (IL-10) and interleukin-6 (IL-6) was investigated in the inflammatory response to Rhodococcus aurantiacus (R. aurantiacus) infection, in which both cytokines act as anti-inflammatory cytokines. Compared with wild-type (WT) counterparts, IL-6 gene-deficient (IL-6(-)/(-)) mice mounted a more robust production of IL-10 and tumor necrosis factor-alpha (TNF-alpha) during the initial phase of infection. Administration of anti-IL-10 antibody resulted in all the mice dying within 3 days post-infection as well as a further elevated TNF-alpha release. In vitro challenge of the macrophages from IL-6(-)/(-) and WT mice with heat-killed R. aurantiacus also showed similar results. Addition of exogenous IL-6 depressed IL-10 and TNF-alpha production by either IL-6(-)/(-) mice or IL-6(-)/(-) mouse macrophages. Likewise, WT mouse macrophages pretreated with anti-IL-10 or anti-IL-6 antibody exhibited increased production of TNF-alpha and IL-6 or IL-10 respectively. Moreover, neutralization of both IL-10 and IL-6 induced a further increase in TNF-alpha production by WT mouse cells. Overall, we conclude that IL-10 is a key element in protecting mice against mortality, and that IL-10 and IL-6 production are negatively regulated by each other although they are additive in suppressing TNF-alpha release in R. aurantiacus-infected mouse model.
Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. yimin@med.hokudai.ac.jp
Yimin
Masashi
M
Kohanawa
Michitaka
M
Ozaki
Sanae
S
Haga
Keiko
K
Fujikawa
Songji
S
Zhao
Yuji
Y
Kuge
Nagara
N
Tamaki
D000193:Actinomycetales Infections / Q000276:immunology*; D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012240:Rhodococcus / Q000276:immunology*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10