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blood cell counts of 100 cells/mm3 or less were recorded; lymphocytes were the first to disappear; and granulocytes were also severely affected but lagged behind the lymphocytes in their rate of decrease. Not all cases demonstrated a sharp decline in white blood cell count, but all casualties with an extremely low leukocyte count died. Infection was a dominant feature, as it was among sulfur mustard casualties during the Iran-Iraq conflict in 1984 and 1986. These patients experienced leukopenia accompanied by total bone marrow aplasia, which included extensive losses of myeloid stem cells (Balali, 1986; Eisenmenger et al., 1991). These findings are further evidence of an association between suppression of immunologic functions and an increased incidence of infectious disease.

In one of the few studies of long-term effects, Zandieh and colleagues (1990) measured the cell-mediated immunity in three groups of Iranians exposed to sulfur mustard: (1) three months to two years after exposure; (2) one to two years after exposure; and (3) two years after exposure. In comparison to normal controls, T lymphocytes showed a significant decrease of 50 percent in all three groups; helper-inducer T cells were significantly decreased in 52 percent of the first and second groups; and T suppressor cells were increased in 53 percent of the first group and 22 percent of the second and third groups. These measurements indicate that depression of the cell-mediated immunity was observed one, two, and three years after exposure to sulfur mustard. Several recent case reports from the Bahar Medical Laboratory in Tehran, Iran, describe similar long-term effects: about 100 patients exposed to sulfur mustard were observed for a year, and the investigator found alterations in B and T lymphocytes. In addition, the phagocytic activity of these patients was reduced to 20 percent of that of a normally functioning immune system (Balali, 1986).

The search for chemical agents with antitumor activities has provided another clue that sulfur and nitrogen mustards are immunotoxic. As alkylating agents, they form covalent linkages with biologically important molecules, resulting in disruption of cell function, especially cell division. As a result, these agents are particularly toxic to rapidly proliferating cells including neoplastic, lymphoid, and bone marrow cells. Because of these immunosuppressive effects, sulfur and nitrogen mustards have particular clinical importance. Nitrogen mustards were the first nonhormonal agents to show significant antitumor activities in humans, producing dramatic tumor regression in lymphoma patients (Colvin and Chabner, 1990). The significance of the immunosuppression produced by alkylating agents in the setting of cancer therapy is uncertain. The major concerns are (1) the danger of increased susceptibility to infection in the immunosuppressed host and (2) the potential interference with a host immune response to the

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