An Interleukin‐6–Related Systemic Inflammatory Syndrome in Patients Co‐Infected with Kaposi Sarcoma–Associated Herpesvirus and HIV but without Multicentric Castleman Disease
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Open Access
- 1 August 2010
- journal article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 51 (3), 350-358
- https://doi.org/10.1086/654798
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.Keywords
This publication has 38 references indexed in Scilit:
- Aids-related malignanciesNature Reviews Cancer, 2002
- Prevalence of Kaposi's sarcoma‐associated herpesvirus infection in sex workers and women from the general population in SpainInternational Journal of Cancer, 2001
- Kaposi’s Sarcoma-Associated Herpesvirus G Protein-Coupled Receptor Constitutively Activates NF-κB and Induces Proinflammatory Cytokine and Chemokine Production Via a C-Terminal Signaling DeterminantThe Journal of Immunology, 2001
- Serum viral interleukin-6 in AIDS-related multicentric Castleman diseaseBlood, 2001
- Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disordersBlood, 2001
- A quantification of human cells using an ERV-3 real time PCR assayJournal of Virological Methods, 2001
- High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients.2000
- Induction of HHV-8 Lytic Cycle Replication by Inflammatory Cytokines Produced by HIV-1-Infected T CellsThe American Journal of Pathology, 2000
- Differential Viral Protein Expression in Kaposi's Sarcoma-Associated Herpesvirus-Infected Diseases: Kaposi's Sarcoma, Primary Effusion Lymphoma, and Multicentric Castleman's DiseaseThe American Journal of Pathology, 2000
- Inflammatory Cytokines and the Reactivation of Kaposi's Sarcoma-Associated Herpesvirus Lytic ReplicationVirology, 2000