DIRECT STIMULATION OF CYTOKINES (IL-1-BETA, TNF-ALPHA, IL-6, IL-2, IFN-GAMMA AND GM-CSF) IN WHOLE-BLOOD .2. APPLICATION TO RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS

Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1β, TNF-α and IL-6 and low production of IFN-γ, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1β and the sedimentation rate; IL-6 and fibrinogen; TNF-α and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-α and IL-6) and different for IL-1β, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid. This parallel in cytokine production between synovial fluid and whole blood stimulated cells, in RA, can be explained by immune induction occurring in the extraarticular lymphatic system, the immune reaction becoming systemic and articular expression being one of the targets of the stimulated immune cells. © 1992.