An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric …
TS Uldrick, V Wang, D O'Mahony… - Clinical Infectious …, 2010 - academic.oup.com
TS Uldrick, V Wang, D O'Mahony, K Aleman, KM Wyvill, V Marshall, SM Steinberg…
Clinical Infectious Diseases, 2010•academic.oup.comBackground. 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 …
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 …
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.
Oxford University Press