title: An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease.
abstract: BACKGROUND
  Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma (KS) and multicentric Castleman disease (MCD) in human immunodeficiency virus (HIV)-infected patients. Patients with KSHV-MCD develop fevers, wasting, hypoalbuminemia, cytopenias, and hyponatremia that are related to overproduction of KSHV-encoded viral interleukin (IL)-6 (vIL-6) and human IL-6 (hIL-6).
  
  
  METHODS
  We identified 6 HIV-infected patients with KS or serological evidence of KSHV infection who had severe inflammatory MCD-like symptoms but in whom we could not diagnose MCD, and we hypothesized that these symptoms resulted from vIL-6 overproduction. Serum vIL-6 levels were assessed in these 6 patients and compared with levels in 8 control patients with symptomatic KSHV-MCD and 32 control patients with KS. KSHV viral load, serum hIL-6 level, and human IL-10 level were also evaluated.
  
  
  RESULTS
  Patients with inflammatory MCD-like symptoms but without MCD had elevated vIL-6 levels, comparable with levels in patients with symptomatic KSHV-MCD, and had levels that were significantly greater than those in control patients with KS (P = .003). Elevated hIL-6, IL-10, and KSHV viral loads were also comparable to patients with symptomatic KSHV-MCD and significantly greater than those with KS.
  
  
  CONCLUSIONS
  A subset of patients with HIV and KSHV co-infection, but without MCD, can develop severe systemic inflammatory symptoms associated with elevated levels of KSHV vIL-6, IL-6, and KSHV viral loads. Excess lytic activation of KSHV, production of the lytic gene product vIL6, and associated immunologic dysregulation may underlie the pathophysiology of these symptoms. This IL-6-related inflammatory syndrome is important to consider in critically ill patients with HIV and KSHV co-infection.
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute-Frederick, Frederick, MD, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.forename: Victoria
authors.initials: V
authors.lastname: Wang
authors.forename: Deirdre
authors.initials: D
authors.lastname: O'Mahony
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000328:Adult; D005871:Castleman Disease / Q000150:complications* / Q000276:immunology; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000150:complications* / Q000276:immunology / Q000821:virology; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology*; D019562:Viral Load; D014764:Viral Proteins / Q000097:blood / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D014764:Viral Proteins; D016753:Interleukin-10