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Tissue Culture Studies of Cellular Hypersensitivity in Rheumatic Fever

II. The Response of Fibroblasts from Human Skin and Heart to Disintegrated Streptococci and to Crude Filtrates of Streptococcal Cultures¹

From the Department of Preventive Medicine and Public Health, University of Colorado School of Medicine and the Department of Health and Hospitals, Denver, Colorado

Abstract

Human fibroblasts grown from the heart and skin of patients with and without rheumatic heart disease have been compared in their responses to crude streptococcal filtrates and to disintegrated organisms derived from streptococcal strains presumed to have caused rheumatic fever. These test substances were incorporated in nutrient media which contained either pooled serum from normal individuals or serum from patients with active rheumatic fever. Fibroblastic growth was evaluated at the end of the second week of culture.

Fibroblasts grown from the skin and heart responded similarly to the streptococcal products tested. The use of rheumatic in place of normal serum did not alter the response.

Fibroblasts grown from rheumatic individuals were nearly always inhibited by a 3% concentration of streptococcal filtrate, while those from normal individuals were not. While the 1% concentration showed some inhibition of the rheumatic tissues compared to the normal, it was not as definite as that found in the 3% concentration. A concentration of 10% resulted in the inhibition of growth of all tissues tested.

Disintegrated streptococci in final concentrations of 0.1 and 0.2% inhibited fibroblastic growth of tissues from rheumatic patients more frequently than from normal individuals. There was complete suppression or inhibition in all cases with the 1.5% concentration.

While the above conclusions were apparent from the study of the grouped data, there was no "all or none effect," so that it was impossible to determine whether or not an individual specimen was derived from a normal or rheumatic patient. If cellular hypersensitivity to streptococcal antigens does exist in fibroblasts of rheumatic fever patients, the observations in tissue culture with the methods here described would indicate a subtle rather than a striking phenomenon.

Footnotes

¹ In addition to the acknowledgments which appeared in the previous paper (I), we wish to thank Dr. Henry Swan II, and his staff of the Department of Surgery, and Dr. E. Stewart Taylor and his staff of the Department of Obstetrics and Gynecology of the University of Colorado Medical Center for the surgical specimens used in these experiments.