Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman's disease.
Castleman's disease is a rare B cell lymphoproliferative disorder related to excess interleukin-6 (IL-6)-like activity. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8), which encodes a functional cytokine (vIL-6), has been found in some patients with Castleman's disease. Lymph nodes from 14 HIV-seronegative Castleman's disease patients were compared to hyperplastic lymph nodes from 25 HIV-seronegative patients as well as Kaposi's sarcoma lesions from 48 patients for KSHV infection and vIL-6, human IL-6, and Epstein-Barr virus EBER expression. While all Kaposi's sarcoma tissues examined were polymerase chain reaction-positive and all control lymph nodes were polymerase chain reaction-negative for KSHV, none had detectable vIL-6 expression. Six of 14 (43%) Castleman's tissues were positive for KSHV by polymerase chain reaction and all 6 had evidence of vIL-6 expression by immunohistochemistry. vIL-6-positive Castleman's disease patients generally had the multicentric plasma cell variant form of the disease and had a rapidly fatal clinical course frequently associated with autoimmune hemolytic anemia and gammopathy. In contrast, 7 (88%) of the 8 vIL-6-negative Castleman's disease patients had localized disease and have remained disease-free after therapy. KSHV vIL-6 expression appears to be limited to hematopoietic cells and is not present in Kaposi's sarcoma spindle cells. These data suggest that Castleman's disease is a syndrome of multiple etiologies involving aberrant IL-6 activity from either endogenous or viral sources.
Parravicini
C
C
Department of Pathology, University of Milano, L. Sacco Hospital, Milan, Italy.
Corbellino
M
M
Paulli
M
M
Magrini
U
U
Lazzarino
M
M
Moore
P S
PS
Chang
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005871:Castleman Disease / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D018023:HIV Seronegativity; D019288:Herpesvirus 8, Human / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007120:Immunochemistry; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism*; D008198:Lymph Nodes / Q000821:virology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000032:analysis / Q000378:metabolism*
D004279:DNA, Viral; D015850:Interleukin-6; D014764:Viral Proteins