Tuberculosis


Researchers' work from University of Geneva focuses on tuberculosis immunology



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2007 NOV 19 -- Fresh data on tuberculosis are presented in the report 'Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.' According to recent research published in the journal Immunology, "Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex."

"To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 ±25 ng/ml of serum and 75 ±13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumor necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth," wrote M.L. Olleros and colleagues, University of Geneva.

The researchers concluded: "These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs."

Olleros and colleagues published their study in Immunology (Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance. Immunology, 2007;122(3):350-61).

For additional information, contact M.L. Olleros, University of Geneva, Dept. of Pathology and Immunology and Clinical Pathology, CMU, Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.

The publisher's contact information for the journal Immunology is: Blackwell Publishing Ltd., 9600 Garsington Rd., Oxford OX4 2DG, Oxon, England.

Keywords: Switzerland, Geneva, Tuberculosis Immunology, Cutaneous Tuberculosis, Immunology, Interferon, Mycobacteria, Mycobacterium Tuberculosis.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.