Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid disorders.
Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced by lymphocytes and stimulated monocytes. Little is known about the production and possible role of IL-12 in human lymphoproliferative disorders. We examined IL-12 expression by immunohistochemistry using antibodies recognizing the p40, p35 subunits, and the p70 heterodimeric IL-12 protein, and by Northern blot in lymph nodes from patients with Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), and nonneoplastic lymphoid lesions. In the majority of the HD cases (28 of 34), IL-12 immunoreaction was found in small lymphoid cells cultured around Hodgkin and Reed-Sternberg (H&RS) cells. No IL-12 signal was seen in H&RS cells. Transcripts for IL-12 were found by Northern and dot blot analysis in 13 of 19 (IL-12 p40) and 11 of 19 (IL-12 p35) cases. The HD cases were further examined for the presence of Epstein-Barr virus (EBV) latent membrane protein (LMP-1). All cases with EBV-LMP-1 positivity (22 of 34 cases) also expressed IL-12. No IL-12 immunoreaction was found in neoplastic cells of 33 cases of various NHLs, which were all LMP-1 negative and showed no EBV-genome sequence, as assessed by polymerase chain reaction (PCR). In 24 nonneoplastic lymphoid lesions, few dispersed IL-12 positive cells were seen in the parafollicular area and in the sinus of the lymph node. The marked presence of IL-12 in the majority of HD cases indicates that IL-12 might play a role in the pathobiology of HD, suggesting that this cytokine is involved in EBV-positive HD.
Schwaller
J
J
Laboratory for Clinical and Experimental Research, Berne, Switzerland.
Tobler
A
A
Niklaus
G
G
Hurwitz
N
N
Hennig
I
I
Fey
M F
MF
Borisch
B
B
D015415:Biomarkers / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology / Q000821:virology*; D006801:Humans; D006965:Hyperplasia; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008199:Lymphadenitis / Q000235:genetics* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000473:pathology; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000032:analysis
D015415:Biomarkers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014763:Viral Matrix Proteins; D018664:Interleukin-12