In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice.

Abstract

The production of immunosuppressive cytokines, such as IL-10 and TGF-beta, has been documented in individuals diagnosed with active tuberculosis. In addition, IL-10 production is increased within the lungs of mice that have chronic mycobacterial infection. Therefore, we hypothesized that the down-regulatory properties of IL-10 might contribute to the reactivation of chronic Mycobacterium tuberculosis infection in mice. To determine the influence of IL-10 on the course of infection, transgenic mice producing increased amounts of IL-10 under the control of the IL-2 promotor were infected with M. tuberculosis via the respiratory route. Mice that overexpressed IL-10 showed no increase in susceptibility during the early stages of infection, but during the chronic phase of the infection showed evidence of reactivation tuberculosis with a highly significant increase in bacterial numbers within the lungs. Reactivation was associated with the formation of macrophage-dominated lesions, decreased mRNA production for TNF and IL-12p40, and a decrease in Ag-specific IFN-gamma secretion. These data support the hypothesis that IL-10 plays a pivotal role during the chronic/latent stage of pulmonary tuberculosis, with increased production playing a potentially central role in promoting reactivation tuberculosis.

• Authors: Joanne Turner, Mercedes Gonzalez-Juarrero, Debi L Ellis, Randy J Basaraba, Andre Kipnis, Ian M Orme, Andrea M Cooper
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 11 Pg. 6343-51 (Dec 01 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12444141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD11a Antigen
• Interleukin-12 Subunit p40
• Protein Subunits
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Interleukin-10
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• CD11a Antigen (metabolism)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Chronic Disease
• Colony Count, Microbial
• Immune Tolerance
• Intercellular Adhesion Molecule-1 (metabolism)
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis, genetics)
• Interleukin-12 (genetics)
• Interleukin-12 Subunit p40
• Lung (immunology, microbiology, pathology)
• Macrophages (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Transgenic
• Mycobacterium tuberculosis (isolation & purification)
• Protein Subunits (genetics)
• RNA, Messenger (genetics, metabolism)
• Tuberculosis, Pulmonary (etiology, genetics, immunology, pathology)
• Tumor Necrosis Factor-alpha (genetics)