Role of IL-6 in Mycobacterium avium--associated immune reconstitution inflammatory syndrome

The Journal of Immunology : Official Journal of the American Association of Immunologists
Daniel L BarberAlan Sher

Abstract

Immune reconstitution inflammatory syndrome (IRIS) is a major adverse event of antiretroviral therapy in HIV infection, and paradoxically occurs as HIV viremia is suppressed and CD4 T cell numbers recover. IRIS reflects pathogenic immune responses against opportunistic infections acquired during the period of immunodeficiency, but little is understood about the mechanisms of inflammatory pathology. In this study, we show that IL-6 and C-reactive protein levels transiently rise at the time of the IRIS event in HIV-infected patients, unmasking Mycobacterium avium complex infection after starting antiretroviral therapy. To directly test the role of IL-6 in IRIS pathology, we used a model of experimentally inducible IRIS in which M. avium-infected T cell-deficient mice undergo a fatal inflammatory disease after reconstitution with CD4 T cells. We find that IL-6 neutralization reduces C-reactive protein levels, alleviates wasting disease, and extends host survival during experimental IRIS. Moreover, we show that combined blockade of IL-6 and IFN-γ further reduces IRIS pathology, even after the onset of wasting disease. The combination of these clinical and experimental-model data show that the IL-6 pathway is not only a biomarker of...Continue Reading

References

Sep 21, 2001·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·P PriceM A French
Sep 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne BourgaritUNKNOWN PARADOX Study Group
Sep 8, 2010·The European Respiratory Journal·R TadokeraR J Wilkinson
Jan 11, 2012·Nature Reviews. Microbiology·Daniel L BarberAlan Sher
Mar 22, 2012·The Medical Journal of Australia·Martyn A H French
Jun 16, 2012·American Journal of Respiratory and Critical Care Medicine·Graeme MeintjesRobert J Wilkinson
Jun 21, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Anali Conesa-BotellaKatalin A Wilkinson
Jul 17, 2012·Cell Metabolism·Kenneth C H FearonDenis C Guttridge
Oct 26, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Suzaan MaraisRobert J Wilkinson
Nov 7, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Katsutoshi AndoKazuhisa Takahashi

❮ Previous
Next ❯

Citations

Dec 10, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Yingda L XieSarah K Browne
Nov 28, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Shruthi RavimohanGregory P Bisson
Apr 17, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Mao LiMasako Shimamura
Oct 2, 2015·Seminars in Immunopathology·Rachel P J LaiRobert J Wilkinson
Oct 14, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bofeng LiTerrence L Geiger
Jan 4, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Radha GopalJay K Kolls
Sep 25, 2019·The American Journal of Tropical Medicine and Hygiene·Eriko KashiharaHiroshi Koyama
Feb 16, 2021·Frontiers in Immunology·Shilpa NaikRupak Shivakoti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cachexia & Brown Fat

Cachexia is a condition associated with progressive weight loss due to severe illness. In cancer patients, it is proposed to occur as a result of tumor-induced energy wasting. Several proteins have been implicated in browning and depletion of white adipose tissue. Here is the latest research on cachexia and brown fat.

Cardiac Cachexia

Cardiac cachexia is a syndrome associated with the progressive loss of muscle and fat mass. It most commonly affects patients with heart failure and can significantly decrease the quality of life and survival in these patients. Here is the latest research on cardiac cachexia.