Studies on the Effect of Triton (Wr-1339) on Guinea Pig Tissues

Abstract

Triton WR-1339, while not bacteriostatic for virulent tubercle bacilli in vitro, has the ability to suppress tuberculosis in experimental animals (1-3).I n the course of studies in this laboratory on the effect of triton on guinea pig tissues it was noted that leucocytes exposed to the detergent either in vitro or in vi~o showed an increased resistance to disruption b y acetone and b y sonic vibration (4). Since surface-active agents chemically similar to triton are known to depress tuberculin sensitivity in guinea pigs (5) it seemed pertinent to determine whether it has any effect on the resistance of leucocytes to another form of trauma, namely in vitro eytolysis b y tuberculin (6).Materials and Methods 8urJace.-Aeti~e Agent.--Triton WR-1339 x was used throughout these studies. For injection of guinea pigs, a 12.5 per cent solution was prepared in 0.16 ~ sodium chloride and sterilized in the autoclave. Treated animals were given triton in a dose of 300 nag. per kg. of body weight. Control animals received an equal volume of saline. Injections were made subcutaneously in the groin.An/reals and D/eI.--An the guinea pigs used in this study were albino males weighing between 300 and 400 gin. They were fed daily with a stock diet of commercial pellets supplemented with fresh cabbage. The ~nlmals were sensitized by a single intramuscular injection of 1.0 cc. of sterile paraffin oil containing 5 rag. of heat-killed human type tubercle bacilli (I-I37Rv). Intradermal skin tests were done with 5 #g. of PPD (Sharp and Dolnne).Leucocyte Cytolysis Tests (7).--Heparinized blood samples were taken from adequately sensitized guinea pigs by cardiac puncture 48 hours after a tuberculin skin test. Aliquots (0.4 cc.) of blood were transferred to each of two siliconized serologic tubes. To one tube was added 0,1 co. of 0.16 u sodium chloride; to the other was added 0.1 cc. (5/~g.) of PPD dissolved in 0.16 J~ sodium chloride. The contents of the tubes were well mixed and total leucocyte counts were made using an AO Spencer hemacytometer. The tubes were then placed on a 37°C. water bath and mechanically shaken at a constant rate for 2 hours, after which a second leucocyte count was made. The PPD decrement was calculated as the per cent change in the tuberculin tube minus the per cent change in the saline control tube. In certain instances variations of this technique had to be employed, details of which will be described later.

Effect of Triton WR-1339 on Experimental Allergic Encephalomyelitis in Guinea Pigs

“…The dosage levels used were within the range of those which have been shown to be capable of suppressing both tuberculin skin hypersensitivity and the in vitro cytolysis of tuberculin sensitive leucocytes by tuberculin (8). As mentioned earlier, the skin reactions that have been found to accompany allergic encephalomyelitis in experimental animals have certain features suggesting delayed-type hypersensitivity to central nervous system tissue.…”

“…The most dramatic effects of triton at the cellular level include its ability to obliterate the lytic effect of tuberculin on perpheral blood leucocytes from tuberculin-hypersensitive animals (8) and block the cellular passive transfer of tuberculin hypersensitivity (9). If "cellular hypersensitivity" prevails in EAE in guinea-pigs, the results of the present study suggest, but do not necessarily prove, that it (a) differs fundamentally from the classical tuberculin type or (b) plays no role in the pathogenesis of the disease.…”

“…Triton WR-1339, a non-ionic surface-active agent, has been found to suppress tuber culin skin hypersensitivity (8), obliterate the lytic effect of tubercu lin on peripheral blood leucocytes from tuberculin sensitive animals (8), and block the cellular passive transfer of tuberculin hypersensi tivity (9). In view of these findings it seemed of interest to determine whether triton would have an effect on the course of EAE in guineapigs.…”

Effect of Bacterial Endotoxin on Leucocytes of Tuberculin Sensitive Hosts

“…The administration of triton YVR-1339, a surface-active agent, 48 hours prior to collection of blood has been found to block the in vitro cytotoxic effect of PPD on leucocytes from tuberculin sensitive guinea-pigs (12). Preliminary attempts to determine whether or not the increased susceptibility of leucocytes from tuberculin sensitive hosts to both PPD and bacterial endotoxin is mediated by a com mon mechanism involved the use of triton.…”

Detergent inhibits 70–90% of responses to intravenous endotoxin in awake sheep

“…Cornforth and associates (6) tested tyloxapol and several related polymers as a method to suppress acute tuberculosis infections in mice. A more thorough study of tyloxapol's possible mechanism of action was published in 1958 (21). Tyloxapol is also used in humans as part of synthetic lung surfactant (37,42).…”