Gérald Streit

The Contribution of Adipose Tissue and Adipokines to Inflammation in Joint Diseases

Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases.

Infectious Complications with Anti-TNFα Therapy in Rheumatic Diseases: A Review

TNFa plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFα antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFα therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFα inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFα inhibitors related infections were described in the randomized clinical trials, and were then declared to postmarketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFα antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFα inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.

Agents anti-TNFα et traitement des spondylarthropathies

Les agents anti-TNFα ont demontre une efficacite clinique sans egal jusqu’alors dans la spondylarthrite, ayant conduit a l’obtention d’une AMM dans cette indication. La tolerance et les precautions d’utilisation sont identiques a celles des autres indications de ces agents biologiques. L’efficacite se manifeste sur tous les aspects cliniques de la maladie, les parametres de l’inflammation biologique et IRM. Cependant, l’effet structural radiologique n’est pas formellement demontre a ce jour. Certains facteurs predictifs de bonne reponse sont identifies, en particulier une CRP elevee a l’inclusion. Certaines questions concernant l’utilisation en pratique restent ouvertes et justifient des etudes complementaires.