Inhibition of p38 MAPK in combination with ART reduces SIV-induced immune activation and provides additional protection from immune system deterioration

PLoS Pathogens
Omkar ChaudharyA Aldovini

Abstract

Differences in immune activation were identified as the most significant difference between AIDS-susceptible and resistant species. p38 MAPK, activated in HIV infection, is key to induction of interferon-stimulated genes and cytokine-mediated inflammation and is associated with some of the pathology produced by HIV or SIV infection in AIDS-susceptible primates. As small molecule p38 MAPK inhibitors are being tested in human trials for inflammatory diseases, we evaluated the effects of treating SIV-infected macaques with the p38 MAPK inhibitor PH-797804 in conjunction with ART. PH-797804 had no side effects, did not impact negatively the antiviral immune response and, used alone, had no significant effect on levels of immune activation and did not reduced the viremia. When administered with ART, it significantly reduced numerous immune activation markers compared to ART alone. CD38+/HLA-DR+ and Ki-67+ T-cell percentages in blood, lymph node and rectal CD4+ and CD8+ T cells, PD-1 expression in CD8+ T cells and plasma levels of IFNα, IFNγ, TNFα, IL-6, IP-10, sCD163 and C-reactive protein were all significantly reduced. Significant preservation of CD4+, CD4+ central memory, CD4+/IL-22+ and CD4+/IL-17+ T-cell percentages and improve...Continue Reading

References

Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T W ChunA S Fauci
Oct 9, 1999·The Journal of Biological Chemistry·S UddinL C Platanias
Feb 17, 2000·Trends in Cell Biology·M Chatterjee-KishoreG R Stark
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P BostikA A Ansari
May 17, 2001·The Journal of Biological Chemistry·I A MayerL C Platanias
Mar 28, 2002·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Leonard H CalabreseUNKNOWN AIDS Clinical Trials Group 334 Investigators
Apr 6, 2002·Journal of Neurovirology·Ned SacktorLeon Epstein
May 22, 2003·The Journal of Biological Chemistry·Fatima LekmineLeonidas C Platanias
Jan 27, 2004·The American Journal of Pathology·Sheila A BarberM Christine Zink
Aug 17, 2004·Immunity·Kerstin WolkRobert Sabat
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ziye SuiSanjay B Maggirwar
Jun 27, 2006·Nature Reviews. Immunology·Jonathan D Ashwell
Jun 1, 2007·Journal of Virology·John T LoffredoDavid I Watkins
Feb 12, 2008·Nature Medicine·Shean J AujlaJay K Kolls
Mar 18, 2009·Immunological Reviews·Mercedes Rincón, Roger J Davis
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yoshiaki NishimuraMalcolm A Martin
Jul 1, 2009·The Journal of Experimental Medicine·Geethanjali PickertChristoph Becker
Aug 12, 2009·Trends in Molecular Medicine·Lydia R CoulthardSusan A Burchill
Sep 2, 2009·The Journal of Pharmacology and Experimental Therapeutics·Heidi R HopeJoseph B Monahan

❮ Previous
Next ❯

Citations

Aug 26, 2021·Retrovirology·E A Nickoloff-BybelP J Gaskill

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
biopsies
biopsy
PMA
ELISA
Assay

Software Mentioned

FlowJo
FACSDIVA
GraphPad Prism

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.