Up-regulation of granulomatous inflammation in interleukin-6 knockout mice infected with Rhodococcus aurantiacus.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print Cited Medium: Print ISSN: 0019-2805 (Print) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE

Original Publication: Oxford : Blackwell Scientific Publications

Actinomycetales Infections/*immunology ; Granuloma/*immunology ; Interleukin-6/*immunology ; Rhodococcus/*immunology; Actinomycetales Infections/pathology ; Animals ; Antibodies, Monoclonal/immunology ; Enzyme-Linked Immunosorbent Assay/methods ; Granuloma/pathology ; Immunosuppression Therapy ; Inflammation/immunology ; Inflammation/pathology ; Interferon-gamma/analysis ; Interferon-gamma/immunology ; Interleukin-6/analysis ; Kinetics ; Liver/immunology ; Liver/pathology ; Mice ; Mice, Knockout ; Necrosis ; Rhodococcus/growth & development ; Spleen/immunology ; Tumor Necrosis Factor-alpha/analysis ; Tumor Necrosis Factor-alpha/immunology ; Up-Regulation/immunology

After intravenous injection of Rhodococcus aurantiacus normal mice develop non-necrotic granulomas, the formation of which is dependent on endogenous interferon-gamma (IFN-gamma). In the early phase of R. aurantiacus infection a high level of endogenous interleukin-6 (IL-6) is detected in the spleen extracts, though its importance is unknown. Using IL-6 knockout (IL-6-/-) mice, we studied the role of IL-6 in granulomatous inflammation induced by R. aurantiacus. The size of granulomas generated in IL-6-/- mice was significantly larger than that of wild-type (IL-6+/+) mice at 2 weeks postinjection (p.i). Moreover, central necrosis of the granuloma was observed in IL-6-/- mice but not in IL-6+/+ controls. Titres of endogenous IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) were markedly increased in the spleens and livers of IL-6-/- mice in comparison with IL-6+/+ mice at days 1 through 3 p.i. In vivo administration of either an anti-IFN-gamma monoclonal antibody (mAb) or anti-TNF-alpha mAb to IL-6-/- mice reduced the number and size of granulomas, and prevented formation of necrotic granulomas. In addition, the production of endogenous IFN-gamma and TNF-alpha in the early phase of R. aurantiacus infection by IL-6-/- mice was suppressed by treatment with recombinant IL-6 (rIL-6). This suppression of IFN-gamma and TNF-alpha production was followed by a reduction in the number and size of central necrotic granulomas at 2 weeks p.i. These findings suggest that overproduction of IFN-gamma and TNF-alpha induces central necrotic granuloma formation in IL-6-/- mice, and that IL-6 down-regulates granulomatous inflammation reaction in response to R. aurantiacus infection by modulating production of IFN-gamma and TNF-alpha.

J Immunol. 1994 Jun 1;152(11):5375-80. (PMID: 8189056)
Infect Immun. 1994 Jul;62(7):2818-24. (PMID: 7911785)
Immunology. 1994 Jul;82(3):361-4. (PMID: 7959868)
Immunobiology. 1994 Oct;191(4-5):369-77. (PMID: 7713550)
J Immunol. 1995 Jun 1;154(11):5969-76. (PMID: 7751640)
Infect Immun. 1995 Jun;63(6):2262-8. (PMID: 7768607)
Microbiol Immunol. 1995;39(7):499-507. (PMID: 8569535)
J Immunol. 1997 Oct 1;159(7):3565-73. (PMID: 9317156)
Immunology. 1997 Dec;92(4):413-21. (PMID: 9497481)
Cell Immunol. 1998 Aug 25;188(1):64-72. (PMID: 9743559)
Immunol Cell Biol. 1998 Dec;76(6):542-9. (PMID: 9893032)
Lab Invest. 1999 Apr;79(4):379-86. (PMID: 10211990)
J Immunol. 1999 Jun 1;162(11):6740-6. (PMID: 10352293)
J Biomed Sci. 1999 Sep-Oct;6(5):349-56. (PMID: 10494042)
J Med Microbiol. 2001 Aug;50(8):688-94. (PMID: 11478672)
J Exp Med. 1984 May 1;159(5):1560-5. (PMID: 6425450)
J Exp Med. 1987 Aug 1;166(2):589-94. (PMID: 3110355)
Infect Immun. 1989 Nov;57(11):3331-7. (PMID: 2509360)
Annu Rev Immunol. 1990;8:253-78. (PMID: 2188664)
Immunology. 1990 Sep;71(1):139-41. (PMID: 2120128)
Infect Immun. 1992 Feb;60(2):523-8. (PMID: 1730485)
Immunol Rev. 1992 Jun;127:5-24. (PMID: 1387110)
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3725-9. (PMID: 8097322)
Infect Immun. 1993 Jul;61(7):2872-8. (PMID: 8514390)
Nature. 1994 Mar 24;368(6469):339-42. (PMID: 8127368)
J Exp Med. 1994 May 1;179(5):1529-37. (PMID: 8163936)

0 (Antibodies, Monoclonal)
0 (Interleukin-6)
0 (Tumor Necrosis Factor-alpha)
82115-62-6 (Interferon-gamma)

Date Created: 20031125 Date Completed: 20040127 Latest Revision: 20211203

20240829

PMC1783069

10.1111/j.1365-2567.2003.01762.x

14632648