PMID- 24337386
OWN - NLM
STAT- MEDLINE
DCOM- 20140428
LR  - 20220330
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 2
DP  - 2014 Jan 15
TI  - Role of IL-6 in Mycobacterium avium--associated immune reconstitution 
      inflammatory syndrome.
PG  - 676-82
LID - 10.4049/jimmunol.1301004 [doi]
AB  - 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-gamma 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 
      mycobacterial IRIS but also a major mediator of pathology distinct from IFN-gamma and 
      may be a useful target for therapeutic intervention.
FAU - Barber, Daniel L
AU  - Barber DL
AD  - T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute 
      of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 
      20892;
FAU - Andrade, Bruno B
AU  - Andrade BB
FAU - McBerry, Cortez
AU  - McBerry C
FAU - Sereti, Irini
AU  - Sereti I
FAU - Sher, Alan
AU  - Sher A
LA  - eng
GR  - T32 AI007610/AI/NIAID NIH HHS/United States
GR  - ZIA AI001171-02/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20131211
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-6)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antiretroviral Therapy, Highly Active/adverse effects
MH  - C-Reactive Protein/immunology/metabolism
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Female
MH  - HIV Infections/immunology/metabolism
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*immunology/metabolism
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-6/*immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Middle Aged
MH  - Mycobacterium avium/*immunology
MH  - Mycobacterium avium-intracellulare Infection/*immunology/metabolism
PMC - PMC3947368
MID - NIHMS541615
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2013/12/18 06:00
MHDA- 2014/04/29 06:00
PMCR- 2015/01/15
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/04/29 06:00 [medline]
PHST- 2015/01/15 00:00 [pmc-release]
AID - jimmunol.1301004 [pii]
AID - 10.4049/jimmunol.1301004 [doi]
PST - ppublish
SO  - J Immunol. 2014 Jan 15;192(2):676-82. doi: 10.4049/jimmunol.1301004. Epub 2013 
      Dec 11.