Profiles of Cytokines (TNFα and IL-6) and Acute Phase Proteins (CRP and α1AG) related to the Disease Course in Patients with Systemic Lupus Erythematosus

Abstract

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukin profiles. Significantly elevated TNF alpha levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNF alpha were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNF alpha and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised alpha 1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNF alpha and IL-6 and also between the different cytokine (TNF alpha and IL-6) levels and acute phase protein (CRP and alpha 1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNF alpha and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

“…[15][16][17][18][19] Consistent with data from other labs, we report here that SLE patients have increased serum TNF-a levels. [43][44][45] TNF-a, a common marker for the activation status of macrophages and DCs, is primarily secreted by activated monocytes/macrophages and may induce the increased expression of Tim-4, thus promoting Th2 cell proliferation via interaction with Tim-1.…”

“…These results indicate that TNF-a plays an important role in the development of SLE, which is consistent with data from other labs. 16,17 We also found a positive correlation between Tim-4 mRNA levels in PBMCs and TNF-a concentrations in serum in SLE patients (P,0.05, r50.4204) (Figure 3b). …”

“…[12][13][14] Increased levels of inflammatory factors, such as IL-17 and tumor necrosis factor (TNF)-a, are detected in the serum from patients with SLE. [15][16][17][18][19] Macrophages, a major cellular constituent of innate immunity and an effective antigen presenting cell (APC) for bridging innate and adaptive immunity, have been widely linked to lupus development. Existing studies focus mainly on defects in macrophage or dendritic cell (DC) phagocytosis, resulting in accumulation of apoptotic debris leading to an array of autoimmune phenomena.…”

Acute Phase Proteins in Prototype Rheumatic Inflammatory Diseases

“…These data could not be explained by changes in disease course or therapy influences. It was concluded that other factors (other than TNF-α and IL-6) may play a role in the regulatory pathway of the APR in SLE (Meijer, Huysen et al 1993). …”

A TNFR2 3′ flanking region polymorphism in systemic lupus erythematosus

“…Serum levels of pro-inflammatory cytokines such as IL-1, IL-6, and TNF␣ have been found to correlate with SLE disease activity in most studies, [1][2][3][4][5][6] suggesting that they may represent a driving force behind disease progression or pathology. In addition, certain studies have demonstrated increased production of these cytokines by peripheral blood mononuclear cell cultures spontaneously or after stimulation, suggesting that cells from these patients may have a generalized increased capacity for the production of pro-inflammatory cytokines.…”