Reciprocal action of interferon-gamma and interleukin-4 promotes granulomatous inflammation induced by Rhodococcus aurantiacus in mice.
An intravenous injection of Rhodococcus aurantiacus to mice causes granulomatous inflammation dependent on endogenous interferon-gamma (IFN-gamma). The present study examined the role of endogenous interleukin-4 (IL-4) on granulomatous inflammation. Endogenous IL-4 in the spleen extracts was not detected during the phase of granuloma formation by enzyme-linked immunosorbent assay (ELISA). However, IL-4 protein level was elevated during the phase of granuloma regression. IL-4 mRNA expression in the livers and spleens was also elevated during the phase of granuloma regression. In addition, IL-4 levels during the phase of granuloma formation were increased by treatment with anti-IFN-gamma monoclonal antibody (mAb), suggesting that endogenous IFN-gamma might inhibit IL-4 production during the phase of granuloma formation. Administration of anti-IL-4 mAb on weeks 3 and 4 after the inoculation inhibited the regression of granulomas and augumented IFN-gamma level at 5 weeks. Endogenous IFN-gamma was produced by CD4+ T cells during the phase of granuloma regression and endogenous IL-4 was produced by both CD4+ and CD8+ T cells. These findings suggest that during the phase of granuloma formation endogenous IL-4 might be inhibited by IFN-gamma, while during the phase of granuloma regression endogenous IL-4 might play a crucial role in the reduction of granulomas and IFN-gamma production.
Asano
M
M
Department of Microbiology, Hokkaido University School of Medicine, Sapporo, Japan.
Kohanawa
M
M
Minagawa
T
T
Nakane
A
A
D000193:Actinomycetales Infections / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012240:Rhodococcus; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma