Experimenteller Rotlauf bei verschiedenen Spezies als Modell einer systemischen Bindegewebskrankheit I. Systemische vaskuläre Prozesse bei der Organmanifestation

Abstract

Introduction The similarities between erysipelas in animals and rheumatic diseases in man have been discussed since the work of Nieberle (1931) . The present work sets out to investigate the course of organ manifestations in pigs, rats, and mice using germ-free or specific pathogen-free experimental animals. Particular consideration will be given to the initial systemic vascular processes as well as to the significance of the erysipelas antigen. Material and methods In several experiments, a total of 166 pigs — partly gnotobiotic or specific pathogen-free animals — 37 specific pathogen free Wistar rats and 57 albino mice were orally and/or parenterally infected with standardized erysipelas strains of serotype B. Clinical examination post infection were carried out with the EKG and by x-raying the joints of the extremities. All large parenchymatous organs, as well as heart valves, aorta and synovia were examined histologically in paraffin sections. In mice and rats, joints of the extremities were embedded in toto in metacrylate. Besides various histological staining methods, histochemical reactions were used to demonstrate mucopolysaccharides and fibrin. The myocardium, central nervous system and synovia of several joints were examined with the electron microscope. In the pig, immunohistological methods demonstrating the presence of fibrin, complement and IgG, as described by Seidler et al. (1971) and Trautwein et al. (1972) , were used. Results The most important changes in joints, heart valves, heart musculature and blood vessels occur during the early bacteriemic phase. A distinct sticking effect develops in the mouse 3.5 hours p.i., in the rat 24 hours p.i., and in the pig 36 hours p.i., Simultaneously, hyaline thrombi occur in capillaries and venules; these are seen as parallel, loosely-packed fibrin fibers in the electron microscope. With the aid of immunofluorescence fibrin, IgG and complement C 3 can also be demonstrated here. Exudates rich in fibrin develop parallel to the microthrombosis. In pigs and rats vascular and myocardial necroses develop 2 to 3 days p.i. The mice do not survice the 3rd day p.i. 39% of the pigs showed edema and mesenchymal activation of varying intensity in the heart valves between the 3rd and 8th day p.i. Besides the insudation of the valves, endocardial thromboses developed in 80% of the mice. Endocarditis, and in addition large aortic thromboses were recognized in more than 50% of the rats. As early as the 4th day p.i., coagulopathy, angionecrosis and exudation led to acute arthritic symptoms. The synovial lining cells are covered with fibrin and begin to proliferate. Increase in the matrix and fibroblast-activation are found in the periarticular connective tissue. Finally, granulation tissue develops which leads to formation of a pannus and destruction of the joint cartilage. Discussion Connective tissue activation caused by erysipelas manifests itself in sites predisposed for rheumatic changes such as joints, heart valves, myocardium and blood vessels. The changes occur even before immune factors could have become pathogenetically effective. Not the bacterial colonization of the connective tissue but rather a coagulopathy together with fibrinous exudation is seen as the intrinsic starter mechanism. The experimental studies suggest that the systemic connective tissue activation is induced by diapedesis of blood plasma, i.e., fibrin deposition in the tissues.