Increased interferon-gamma (IFN-γ), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE)

Abstract

SUMMARYCytokines are important regulators of lymphocyte function in SLE. However, the profile of Th1 and Th2 cytokines produced by circulating lymphocytes in human SLE has not been clearly elucidated. The aim of the present study was to characterize the gene expressions of the Th1-type cytokine IFN-g, and the Th2-type cytokines IL-10 and IL-4 in PBMC of 15 patients with SLE and 10 healthy individuals by a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Our results showed that expression of IFN-g (P 0´0004) and IL-10 (P 0´002) transcripts were significantly increased in PBMC of patients with SLE compared with healthy controls. By contrast, expression of IL-4 transcripts in PBMC of patients with SLE was significantly decreased compared with the healthy controls (P 0´0008). Primary sources of IL-10 were B cells and monocytes, with variable contribution of T cells as detected in various fractions of PBMC of patients with SLE (P 0´049). These findings support the hypothesis that the enhanced production of IFN-g by mononuclear cells may trigger inflammatory responses, together with the enhanced production of IL-10 resulting in autoantibody production by B cells in human SLE.

IL-10 Regulates Murine Lupus

“…Increased IFN-␥ mRNA and decreased IL-4 gene expression are found in PBMCs taken from SLE patients (5). Th1 cytokines, including IFN-␥, are present in tissue of SLE patients with the most severe disease, with enhanced production of this cytokine by peripheral blood cells and in the kidneys of patients with severe lupus glomerulonephritis, compared with individuals with milder renal disease (6,7).…”

“…This cytokine has been presumed to be an important modulator of disease activity in human SLE. Patients with lupus produce large amounts of , with enhanced gene expression in PBMCs (5), and its serum level correlates with disease activity (19 -21). While the precise role of IL-10 in the pathogenesis of lupus remains uncertain, studies have suggested that this cytokine is pathogenic both in humans and in mice with disease.…”

The genetics of systemic lupus erythematosus: putting the pieces together

“…99 Among SLE patients, the numbers of IL-10-producing cells are increased in the peripheral blood, resulting in these patients having an abundance of pathogenic autoantibodies. [100][101][102] Moreover, lupus-prone mice that are administered recombinant IL-10 develop accelerated autoimmune disease. 103 For these reasons, IL-10 is a possible candidate gene in lupus susceptibility.…”

Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production

“…This may, in turn, affect tolerance against self-antigens and lead to a dysfunction of the immune system. [3][4][5] Large numbers of B-1a cells were found in subjects with chronic periodontitis, Sjö gren's syndrome and rheumatoid arthritis. [6][7][8][9][10] Interleukin (IL)-10 is an important cytokine in the regulation of immune responses and was earlier considered to be mainly anti-inflammatory.…”