Abnormal expression of the IL-6 gene has been suggested to be involved in the pathogenesis of a variety of diseases, especially rheumatoid arthritis, Castleman's disease, mesangial proliferative glomerulonephritis, multiple myeloma and Kaposi's sarcoma.
Pretreatment of KS cells with poly (I:C) for 24 h followed by removal of the poly (I:C) led to high levels of IL-6 secreted into medium that induced proliferation in KS cells.
Four virus proteins similar to two human macrophage inflammatory protein (MIP) chemokines, interleukin-6 (IL-6), and interferon regulatory factor (IRF) are encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 was functional in B9 proliferation assays and primarily expressed in KSHV-infected hematopoietic cells rather than KS lesions.
By immunostaining, mesothelioma cells expressed interleukin-6 and platelet-derived growth factor, which are important for survival of Kaposi's sarcoma cells.
The genome of human herpes virus 8, which is associated with Kaposi's sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6.
While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples.
Colocalization of the viral interleukin-6 with latent nuclear antigen-1 of human herpesvirus-8 in endothelial spindle cells of Kaposi's sarcoma and lymphoid cells of multicentric Castleman's disease.
In addition to the HHV-8 infection, the interleukin-6 promoter polymorphism G-174C is associated with a risk of development of KS in renal transplant recipients.