Comparison of 4,4-Diaminodiphenylsulfone and Its Thymolated Derivative in Experimental Tuberculosis in Guinea Pigs

¹ Section of Bacteriology, Mayo Clinic and Mayo Foundation.

Each of 36 guinea pigs was infected intraperitoneally with virulent tubercle bacilli. After 16 days, six were killed and found to have tuberculous lesions. On the same day, the remaining animals were divided into three groups of 10 animals each, namely controls, those treated with 4,4'-diaminodiphenylsulfone (DDS), and those treated with DDS- thymol. Treatment continued for 116 days, at which time all survivors were killed. Six controls had died by this time. All controls, including four survivors, had extensive tuberculosis.

Of those animals treated with DDS-thymol, two died prematurely; two others died after 53 and 81 days of treatment, respectively, and had extensive lesions. Of the surviving six animals, one had a few residual foci in the liver and lungs and two others had microscopically evident lesions in the lungs only. All had caseous lesions in lymph nodes. None of these animals showed any toxic effect from the drug.

None of the animals given DDS died; four had evidence of pulmonary tuberculous lesions. All had caseous foci in the lymph nodes and enlarged cyanotic spleens with dilated sinusoids and many pigment-laden macrophages.

The administration of DDS-thymol to tuberculous guinea pigs resulted in regression of the disease, but the beneficial effect was less than that of DDS. The hematotoxic effects of DDS, as determined by splenic changes, were not seen in animals given DDS-thymol. It was not determined whether DDS-thymol has a direct action or if it is active because of DDS liberated in vivo.