Henry H. Freedman

Oxisuran, a differential inhibitor of cell-mediated hypersensitivity.

Summary Oxisuran, 2-[(methylsulfinyl)a-cetyl] pyridine, has been shown to suppress allograft rejection in the rodent without causing concomitant suppression of the hemolytic antibody response to sheep erythrocytes. This simple synthetic compound thus differs from presently defined “immunosup-pressants,” such as 6-mercaptopurine with which it has been directly compared, which from their modes of action fail to discriminate between humoral and cell-mediated immune responses. The authors are grateful to Dr. Donald L. Ballantyne, Jr., for making available the data in Table II from his collaborative studies on oxisuran.

INFLUENCE OF OXISURAN, A DIFFERENTIAL INHIBITOR OF CELL-MEDIATED HYPERSENSITIVITY, ON ALLOGRAFT SURVIVAL AND HUMORAL IMMUNITY

SUMMARY Oxisuran, 2-[(methylsulfinyl)acetyl]pyridine, has been shown to suppress allograft rejection in mice, rats, and dogs. Unlike 6-mercaptopurine or azathioprine, oxisuran does not concomitantly suppress humoral antibody production in mice or dogs. The compound is less active in the dog than in the rat, a finding consistent with the different metabolic pathways found in these two species. The toxicology of oxisuran and implications for mechanism of action are discussed.

Effects of thyroidectomy and of thiouracil on adrenal weight and ascorbic acid.

Summary The administration of thiouracil to the male rat results in a pronounced atrophy of the adrenal glands and an initial increase in ascorbic acid concentration in the adrenals followed by a return to normal values. Surgical thyroidectomy produces a less pronounced adrenal atrophy but a greater adrenal inhibition as revealed by a final decrease in adrenal ascorbic acid concentration. The effects of both types of induced hypothyroidism on the adrenals may be prevented by the administration of thyroxin. It is concluded that adrenal ascorbic acid concentrations are reliable indices of adrenocortical activity only if interpreted in terms of change in adrenal size.

Antibody formation at various times after previous treatment of mice with endotoxin.

Summary The effects of sheep red blood cells or endotoxins on numbers of hemolysin-forming spleen cells have been studied in mice previously injected with a small dose of endotoxin. One day after pretreatment the response to sheep red cells was greater than normal and the response to endotoxin was smaller than normal. At 10-12 days after pretreatment, the response to sheep red cells was normal but the response to endotoxin, given alone or together with sheep red cells, was greater than normal. Of 5 endotoxin preparations studied, only a protein-free endotoxin failed to alter reactivity to a subsequent injection of the same endotoxin.

Role of Protein Component of Endotoxin in Modification of Host Reactivity.

Summary The influence of endotoxins of varying nitrogen content on water intake and numbers of hemolysin-forming spleen cells in mice and on delayed skin reactivity in rabbits has been investigated. Pretreatment with an aqueous-ether endotoxin of S. enteritidis results in heightened reactivity to a subsequent test dose of the aqueous-ether or protein-free (Ribi) endotoxin, whereas pretreatment with the protein-free endotoxin fails to modify subsequent reactivity to either endotoxin. Similarly, pretreatment with the Boivin endotoxin of S. abortus equi increases reactivity on subsequent test with the Boivin or Westphal endotoxin, whereas pretreatment with the partially deproteinized Westphal endotoxin does not enhance reactivity to subsequent test with either endotoxin. The implications of these findings for the hypothesis that adult host reactivity to endotoxins is contributed to by an acquired delayed hypersensitivity are discussed.

Inhibition by Endotoxin of the Migration of Peritoneal Exudate Cells from Endotoxin Sensitive Mice

Summary The influence of various bacterial endotoxins on the migration of mouse peritoneal exudate cells has been examined. Pretreatment of cell donors with S. abortus-equi or E. coli endotoxins rendered cells, harvested 10 days later, more susceptible to inhibition by the respective endotoxins. This increased reactivity was not in evidence for cells harvested 5 or 20 days after treatment. Cells from S. marcescens endotoxin treated animals did not exhibit a change in their susceptibility to that endotoxin during the 20-day test period. These findings are entirely consistent with previous in vivo studies supporting the hypothesis that host reactivity to endotoxins has an origin in an acquired hypersensitivity of the delayed type.

Effect of Anti-Hyaluronidase Compounds upon the Response of the Rat to Pituitary Trophic Hormones

Summary Anti-hyaluronidase agents, i.e. phosphorylated hesperidin, d-alphatocopherol phosphate, and chrondroitin sulfate were shown to be capable of increasing the effectiveness of administered pituitary trophic hormones such as follicle stimulating hormone (FSH) and corticotrophin. A four-fold increase in effectiveness of FSH was attained when the hormone was administered together with the anti-hyaluronidase agents as compared to the injection of the gonadotrophin alone. A similar degree of enhancement was obtained with corticotrophin. The augmentation induced by the anti-hyaluronidase compounds is attributed to the decreased rate of absorption of the hormone from the site of injection.