Cytokine production and serum levels in systemic sclerosis

Abstract

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL1-β), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide- or mitogen-induced production of the cytokines, TNF-α, IL1-β, and IFN-γ, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) <3 years duration, and 11 with dcSSc >3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1–2 U/ml) were detected in 10 29 sera tested. Spontaneous production of TNF-α and IL1-β by PBMNC of patients with SSc (829 pg/ml ± 215 SEM and 728 pg/ml ± 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 ± 10 and 34 ± 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-α or IL1-β were seen in patients with early dcSSc. No significant difference in spontaneous IFN-γ production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-γ production by PBMNC was significantly depressed in patients with SSc (103 U/ml ± 18 vs 255 ± 33 U/ml in controls). In vitro-induced production of TNF-α or IL1-β by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.