Experimental Models of Rheumatoid Inflammation

Abstract

Rheumatoid arthritis and allied inflammatory rheumatic diseases have been thought to be due to allergic processes almost since the turn of this century; yet intensive investigation has failed to reveal classical evidence for defined extrinsic antigens at sites of rheumatic inflammation. In the last few decades increasing laboratory evidence has highlighted immunological abnormalities in these disorders and attention has been drawn frequently to clinicopathological similarities with known hypersensitivity or infectious diseases in man and animals. At the present time it is widely held that the different inflammatory rheumatic syndromes arise through genetically based immunopathological responses to microbial infection though it is also conceded that much of the evidence supporting this view is circumstantial. Two principal kinds of derangement have been suggested by which such pathogenetic mechanisms may operate: (i) an inability to eradicate certain microbes or their products from the host and thus from potential sites of rheumatic inflammation; and (ii) a failure to stop a reaction produced by what would normally be regarded as an ephemeral stimulus to the host’s immune system. Herein lies the paradox of immunology and infection in the rheumatic diseases: for whereas the local tissue lesions look like hypersensitivity responses to persisting antigens, the immunological and microbiological evidence which would support this inference is circumstantial.