Effect of Penicillin Treatment on Serum Complement Levels in Acute Rheumatic Fever.

Serum complement levels are determined in various diseases for two main reasons: first, any deviation from normal may be used for differential diagnostic purposes, and secondly, alterations in serum complement levels may be of pathogenetic significance in that they indicate the participation of the complement system in the disease process. In acute rheumatic fever, serum complement levels have been found to deviate significantly from normal. Fischel, Pauli, and Lesh (1949), and Fischel, Frank, Boltax, and Arcasoy (1958) and Williams and Law (1958) reviewed the literature when reporting their own data. Raised levels were found predominantly during the early course of rheumatic fever. Longitudinal studies with repeated complement determinations by Fischel, Pauli, and Lesh (1949) have shown raised levr Is to persist in some cases for up to 7 weeks during and after the course of acute rheumatic fever. In this paper correlation with clinical data indicates that the administration of salicylates does not influence the persistent elevation of serum complement lvels. The effects on complement of treatment with sulphonamides or antibiotics were not correlated. Furthermore, in these studies, serum complement levels were measured at long and irregular intervals which did not permit the observation of transient fluctuations. Therefore, it appeared desirable to study the serum complement levels in a longitudinal fashion with frequent complement determinations, paying special attention to the duration of the illness and various clinical manifestations as well as to treatment. It is the purpose of this paper to describe significant changes in serum complement levels found after starting treatment in forty cases of acute rheumatic fever. Methods Forty patients with acute rheumatic fever were studied clinically and serologically while in the University Hospital, Baltimore, Maryland. Patients were admitted to the study according to the modification of the criteria of Duckett Jones (1944) set forth in the U.K. and U.S. joint reports on rheumatic fever (1955, 1960), and signs and symptoms were assessed and recorded daily. Blood was drawn under sterile conditions at various times from all forty patients with acute rheumatic fever, sera from sixty normal persons serving as controls. Serum was obtained by centrifugation of clotted blood (incubated at room temperature for less than 2 hrs), and was stored at -70° C. Serum complement levels were determined and expressed in C'-H50 haemolytic units according to the technique of Mayer (1961). The haemolytic unit of complement was defined as the amount demonstrated in 1 ml. which will lyse 2 5 x 108 optimally sensitized red cells out of a total of 5 x 10 cells in the presence of optimal Ca++ and Mg++ ions at an ionic strength of0 147 with 1 j hrs incubation at 370 C. in a total volume of 7 5 ml. A "vor-test" using various serum dilutions was employed to make a rough estimate of the point of 50 per cent. haemolysis. The result of this "vor-test" constituted the basis for the main test which was then carried out with four dilutions set up for each serum in duplicate, together with four control tubes. The Beckman Spectrophotometer DB 19 was used at a wavelength of 541 millimicrons. The results were plotted on logarithmic paper and the number of 50 per cent. haemolytic units was calculated. The inclination of the slope of the graph was used as a guide for accuracy. Results were considered acceptable when found within the ±0-02 or 10 per cent. deviation from the mean