Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

Abstract

We have investigated constitutive and phytohaemagglutinin (PHA) + phorbol 12-myristate 13-acetate (PMA)-induced gene expression of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-3, IL-4, IL-10, IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF) in peripheral blood mononuclear cells (PBMCs) of 10 patients with Takayasu's arteritis (TA) and 10 healthy controls by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The constitutive mRNA expression of TNF-α (69.0 ± 4.0%versus 27.5 ± 18.0%; P = 0.001) and IL-4 (60.0 ± 10.0%versus 0%; P = 0.001) was significantly higher in patients than controls; that of IL-3 was comparable in both groups (38.0 ± 6.0%versus 32.0 ± 5.0%; P = 0.651) while no constitutive mRNA expression was observed for the other cytokines studied. The stimulated PBMCs of patients, as compared with the controls, had higher mRNA gene expression of TNF-α (127.0 ± 16.0%versus 54.0 ± 6.0%; P = 0.001), IFN-γ (93.0 ± 13.0%versus 57.0 ± 5.0%; P = 0.032), IL-2 (109.0 ± 13.0%versus 68.0 ± 6.0%; P = 0.015), IL-3 (60.0 ± 8.0%versus 21.2 ± 3.0%; P = 0.045) and IL-4 (68.0 ± 7.0%versus 27.0 ± 7.2%; P = 0.01) The mRNA expression of IL-10 was lower in patients than controls (35.0 ± 8.0%versus 75.0 ± 12.0%; P = 0.022). The GM-CSF mRNA was similar (102.0 ± 6.0%versus 89.0 ± 5.0%; P = 0.475) in both groups. Stimulation of cells with PHA + PMA showed no IL-12 expression but stimulation with lipopolysaccharide induced higher IL-12 mRNA in patients than controls (83.0 ± 14.0%versus 33.0 ± 4.0%; P = 0.005). Our data suggest that an inflammatory cytokine signature exists in TA with a key role for TNF-α, IL-4, IL-10 and IL-12 in different pathological processes of the disease.