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

We have investigated constitutive and phytohaemagglutinin (PHA) + phorbol 12-myristate 13-acetate (PMA)-induced gene expression of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, 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-alpha (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-alpha (127.0+/-16.0% versus 54.0+/-6.0%; P=0.001), IFN-gamma (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-alpha, IL-4, IL-10 and IL-12 in different pathological processes of the disease.