Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity

Abstract

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines.MethodsWe determined levels of IFN-λ1 mRNA in peripheral blood mononuclear cells (PBMC) and serum protein levels in patients with SLE using real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunoassay (ELISA). Further, we detected the concentration of IFN-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and interleukin-8 (IL-8) secreted by PBMC under the stimulation of IFN-λ1 using ELISA.ResultsIFN-λ1 mRNA and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IFN-λ1 mRNA and serum protein levels compared with those with inactive disease as well. Serum IFN-λ1 levels were positively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), anti-dsDNA antibody, C-reactive protein (CRP) and negatively correlated with complement 3. Serum IFN-λ1 levels were higher in SLE patients with renal involvement and arthritis compared with patients without the above-mentioned manifestations. IFN-λ1 with different concentrations displayed different effects on the secretion of the chemokines IP-10, MIG and IL-8.ConclusionsThese findings indicate that IFN-λ1 is probably involved in the renal disorder and arthritis progression of SLE and associated with disease activity. Moreover, it probably plays an important role in the pathogenesis of SLE by stimulating secretion of the chemokines IP-10, MIG and IL-8. Thus, IFN-λ1 may provide a novel research target for the pathogenesis and therapy of SLE.

Interferon (IFN)-λ is a potential mediator in lupus nephritis

“…Increased levels of IFNλ have been demonstrated in patients with SLE, the highest levels were found in patients with renal involvement and arthritis and levels also correlated with disease activity. 7 IFNλ was also expressed in skin lesions from patients with SLE. 8 Although IFNα is considered central in SLE, and recent data support a role also for IFNλ, not much is known about how these cytokines correlate or how they are affected by immunosuppressive treatment in LN.…”

“…6 Some recent studies indicate that IFNλ is involved in the pathogenesis of SLE. Increased levels of IFNλ have been demonstrated in patients with SLE, the highest levels were found in patients with renal involvement and arthritis and levels also correlated with disease activity 7. IFNλ was also expressed in skin lesions from patients with SLE 8…”

IL-29 Enhances LPS/TLR4-Mediated Inflammation in Rheumatoid Arthritis

“…IL-29 (IFNλ1) is the most active cytokine among all type III IFNs. A previous study has implicated that IL-29 was involved in renal disorder and arthritis progression of systemic lupus erythematosus (SLE) through regulating the production of several chemokines [9]. Interestingly, increased level of IL-29 has been observed in patients with rheumatology arthritis (RA) as compared with healthy controls [10].…”

Elevated Serum Levels of Interleukin-29 Are Associated with Disease Activity in Rheumatoid Arthritis Patients with Anti-Cyclic Citrullinated Peptide Antibodies

“…(Kotenko 2011;Liu et al 2012). Examples of the latter include the connective tissue disorders such as RA and systemic lupus erythematosus (Wu et al 2011). Our results showed that serum IL-29 levels in patients with RA were significantly higher compared to HC, suggesting a role for IL-29 in the pathogenesis of RA.…”