An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease.
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.
Uldrick
Thomas S
TS
HIV and AIDS Malignancy Branch, National Cancer Institute-Frederick, Frederick, MD, USA.
Wang
Victoria
V
O'Mahony
Deirdre
D
Aleman
Karen
K
Wyvill
Kathleen M
KM
Marshall
Vickie
V
Steinberg
Seth M
SM
Pittaluga
Stefania
S
Maric
Irina
I
Whitby
Denise
D
Tosato
Giovanna
G
Little
Richard F
RF
Yarchoan
Robert
R
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*
D015850:Interleukin-6; D014764:Viral Proteins; D016753:Interleukin-10