title: Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4⁺ T-cell loss, pathogenic processes that contribute to disease progression.
  
  
  METHODS
  To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody.
  
  
  RESULTS
  Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells. However, compared with untreated rhesus macaques, adalimumab-treated rhesus macaques showed attenuated expression of proinflammatory genes, decreased infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, and weaker antiinflammatory regulatory responses to SIV infection (ie, fewer presumed alternatively activated [ie, CD163⁺] macrophages, interleukin 10-producing cells, and transforming growth factor β-producing cells), along with reduced lymphoid tissue fibrosis and better preservation of CD4⁺ T cells.
  
  
  CONCLUSIONS
  While HIV/SIV replication drives pathogenesis, these data emphasize the contribution of the inflammatory response to lentiviral infection to overall pathogenesis, and they suggest that early modulation of the inflammatory response may help attenuate disease progression.
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, SAIC-Frederick, Maryland, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Tabb
authors.forename: David R
authors.initials: DR
authors.lastname: Morcock
authors.forename: Charles M
authors.initials: CM
authors.lastname: Trubey
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Quiñones
authors.forename: Xing Pei
authors.initials: XP
authors.lastname: Hao
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.forename: Rhonda
authors.initials: R
authors.lastname: Macallister
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Levelle D
authors.initials: LD
authors.lastname: Harris
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Alvord
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
mesh_terms: D000068879:Adalimumab; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008253:Macaca mulatta; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D011897:Random Allocation; D015301:Retroviruses, Simian; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab