INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR MESSENGER-RNA EXPRESSION IN RHEUMATOID-ARTHRITIS - PROLONGED PRODUCTION OF IL-1-ALPHA

  • 1 September 1988
    • journal article
    • research article
    • Vol. 73  (3) , 449-455
Abstract
In rheumatoid arthritis there is a chronic immune and inflammatory reaction which can lead to the destruction of the diseased joint. Cytokine gene expression was studied in synovial cells using cDNA probes specific for human interleukin 1 (IL-1), -.alpha. and IL-1.beta., tumour necrosis factor (TNF), -.alpha. and TNF.beta. (lymphotoxin); protein molecules which induce cartilage degradation and bone resportion. In all cases studied, IL-1 mRNA was present in freshly isolated synovial cells from fluid or membrane. Compared to levels of IL-1 mRNA found in optimally activated normal blood mononuclear cells, the levels of IL-1.alpha. mRNA were high in seven of the nine patients studied, whereas IL-1.beta. mRNA, the dominant form in blood, was relatively lower. TNF.alpha. and TNF.beta. mRNA were also detected. Rheumatoid synovial cells, cultured without any stimulus, continued to express high levels of IL-1.alpha. mRNA for up to 5 days, compared to the 24 h response of activated blood cells; IL-1.beta. mRNA in culture was also prolonged. Cultures of rheumatoid joint cells produced IL-1 bioactivity, with roughly equal amounts of IL-1.alpha. and .beta., as assessed using neutralizing antibodies. TNF bioactivity was also detected which may be of importance as TNF induces the production of IL-1. The finding of these mediators produced in large amounts in active rheumatoid synovial cells suggests that mutually stimulatory cell interactions, mediated by these molecules, may be important in the chronic inflammation and tissue destruction in rheumatoid arthritis.