The action, in vitro and in vivo, of some nitrogen mustards on haemolytic complement.

It has been shown (Boursnell, Francis & Wormall, 1946) that haemolytic complement is rapidly inactivated by small amounts of sulphur mustard (di-2-chloroethyl sulphide; code no. H) and divinyl sulphone. Since the nitrogen mustards have been widely used during recent years in the treatment of some neoplastic diseases, we decided to study the action, in vitro and in vivo, of a typical nitrogen mustard (di-2-chloroethylmethylamine; code no. HN2) on the haemolytic complement of man and some other animals. Haemolytic complement is a complex system containing four functionally distinct components, and it is generally agreed that complement plays an important role in natural immunity and resistance to infection. Although it has not been definitely established that a low blood complement in an animal is associated with a low resistance to infection, many investigators have reported low blood complement titres in some infectious diseases (for the literature see the reviews by Osborn, 1937; Ecker, Seifter & Dozois, 1945; Ecker, 1948). If the therapeutic use of the nitrogen mustards, involving a course of intravenous injections of the drug, were to result in a severe diminution of the blood complement, this loss might have serious ill effects. A considerable amount ofinformation is available about the separation of the four components of complement, and about their stability and general chemical properties, but the mode of action of this complex system is still unknown. It is a relatively labile system associated largely with certain serum globulins, and the inactivation of any one component, for example by mild oxidation or by denaturation, leads to complete loss of haemolytic, bacteriolytic and bactericidal effects. Pillemer & Ecker (1941 a) and Heidelberger (1941) have suggested the use of C'1, C'2, C'3 and C'4 as symbols for the 'midpiece', 'endpiece', and third and fourth components respectively, and this nomenclature is used in the present paper. The main object ofthe present investigations was to determine whether the clinical use of HN2 and related nitrogen mustards is likely to lower seriously