In human lupus patients, the serum IL-6 levels correlated positively with the disease activity and anti-DNA levels.[14, 15] Lymphoblastoid cells isolated from lupus subjects expressed heightened levels of IL-6 while an blockade of IL-6 will result in diminution of anti-dsDNA in vitro.[16] When compared with healthy individuals, B lymphocytes recovered from SLE patients spontaneously generated increased quantity of learn more circulating immunoglobulins. IL-6 blockade significantly abrogated this spontaneous

immunoglobulin secretion, but was restored with exogenous administration of IL-6.[15] It had been shown that B lymphocytes from lupus patients had spontaneous anti-dsDNA production and this autoantibody synthesis ex vivo was predominantly secreted by low density B lymphocytes.[17] One should appreciate that IL-6 can assist these low density B cells from active lupus subjects to differentiate directly into Ig-secreting cells.[17, 18] CD5 expression suppressed BCR signalling in SLE B lymphocytes and IL-6 downregulated CD5 expression via DNA methylation and hence facilitated the activation and expansion of autoreactive B cells in SLE patients.[19] Genetic polymorphisms of the functional interleukin-6 (IL-6) promoter appear to confer susceptibility of SLE in ethnically different populations. For instance, the IL-6–174 Antiinfection Compound Library supplier G/C gene polymorphisms

would predispose to SLE in Caucasians but such observation is less well established in Asians.[20-22] PtdIns(3,4)P2 Apart from its systemic effects, IL-6 was shown to have a tight link with lupus nephritis. Several studies demonstrated elevated urinary IL-6 excretion in patients with active proliferative lupus nephritis who also had high titres of anti-dsDNA antibodies.[23, 24] Moreover, there was enhanced in situ expression of IL-6 along the glomeruli and tubules in lupus nephritis kidneys.[25] In patients with neuropsychiatric manifestation, there was an excessive IL-6 levels in the cerebrospinal fluid.[26] Furthermore, SLE patients with ongoing synovitis (19%) and joint deformities (11%) had raised IL-6 levels and such increase correlated

with other serological markers of SLE such as ESR (Erythrocyte Sedimentation Rate) and anti-dsDNA level.[27] While IL-6 is consistently reported to be upregulated in SLE patients, C-reactive protein (which is ordinarily induced by IL-6) and serum amyloid precursor protein (both being pentraxin group) are typically not elevated, and the risk of secondary amyloidosis is uncommon among SLE patients. Recent data have also showed that in SLE patients have specific defect in responding to IL-6 in terms of pentraxin production.[28] IL-6 and its receptors can serve as biomarkers to monitor disease activity and treatment response. IL-6 release from peripheral blood mononuclear cell (PBMC) was associated with disease activity and treatment response in lupus nephritis patients.