pounds on immune function by simultaneous intramuscular injection of typhoid vaccine and nitrogen mustard into rabbits. The data suggest that the toxicity of nitrogen interferes with or suppresses antibody-forming mechanisms of the lymphocyte.
More recent studies have generally confirmed earlier evidence that laboratory animals exposed to mustards experience changes in cells of the immune system that result in undesirable effects (i.e., immunosuppression, alteration of host defense mechanisms against pathogens and neoplasia). Coutelier and colleagues (1991) noted a marked decrease in the number of spleen cells in mice one week after receiving a relatively high dose of sulfur mustard. B lymphocytes were relatively more affected than T lymphocytes by sulfur mustard; similar results were seen in humans, where toxicity for B lymphocytes led to a decrease in B-cell number following exposure to nitrogen mustard compounds.
Blank and colleagues (1991) compared the immunotoxicity of sulfur mustard and nitrogen mustard on humoral and cell-mediated immunity of mice. The effects on thymic and splenic weight, spleen cell number, and the formation of antibody were similar to earlier laboratory results. Both compounds induced splenic and thymic weight loss. When splenic cellularity was depressed, the total number of cells producing antibody response was decreased. Only when sulfur mustard reached lethal levels were the total spleen cells producing antibody response at a level equivalent to that observed following nitrogen mustard administration. Hence, the immunotoxic effect of nitrogen mustard could be distinguished from general toxicity and was tolerated at a higher dose than was sulfur mustard. Nitrogen mustard had an additional immunotoxic effect of decreasing host resistance to tumor cells that was not observed with sulfur mustard. The reason for these differences is unclear.
Evidence that sulfur mustard causes immunosuppression in humans has emerged from several lines of investigation. The earliest evidence came from clinical observations of humans directly exposed to sulfur mustard during World War I (WWI), who showed significant quantitative and qualitative changes in the circulating elements of the immune system. Stewart (1918) studied 10 fatal cases of mustard poisoning and observed striking depression of bone marrow production of white blood cells. For example, in one case the patient showed a total leukocyte count of 7,630/mm3 on the second day after exposure (gassing), 6,650 on the third day, and 270 on the sixth day, 24 hours before death. In another case a total leukocyte count of 35,000 was measured on the second day after gassing, which dropped to 16,000 on the third day, and to 172 on the seventh day, six hours before death.