Immunopathogenesis and immunotherapy in rheumatoid arthritis: an area in transition.
In years to come, new therapeutic modalities for the treatment of chronic arthritis will be launched for general clinical use. These therapies, until today only used in clinical studies, are based on knowledge obtained from animal models of chronic arthritis. This knowledge not only ushers therapeutic use in humans: in many settings, the animal studies have proven to be irreplacable tools to get insights into the pathogenesis of chronic arthritis. Rheumatoid arthritis (RA) shows a strong linkage of susceptibility to a certain epitope common to some HLA-DR beta chains; this immunogenetic linkage is the strongest evidence for specific, T-cell dependent immunity in the pathogenesis of the disease. Despite intense efforts, no unequivocal proofs of T-cell specificity or oligoclonality have been found in RA. Therapeutic efforts directed against T-cells or T-cell functions have also at the best showed partial effects. As compared to the local production of T-cell cytokines in the joint, monokine production is abundant. Therapies aimed at neutralizing the effects of the cartilage-devastating monokine TNF-a have showed remarkable results in small clinical trials. The possibility of increasing the presence of the regulatory cytokines IL-4, IL-10 and TGF-beta has also been explored, but only in animal studies. Immunology has also shed light on the mode of action of the commonly used 'disease modifying' drugs, and combinations of such drugs have shown increased potentials in recent clinical studies. The possibility of combining traditional anti-arthritic drugs with recent immunological tools seem promising for the future. This review discusses recent advances in the understanding of pathogenesis and delineate new therapeutic approaches for chronic arthritis from the point of view of the immunologically oriented clinician.
Klareskog
L
L
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Rönnelid
J
J
Holm
G
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000502:physiology*
D016207:Cytokines