I. Intravenous Administration of Nitrogen Mustard Alone and with Corticotropin for Rheumatoid Arthritis
NITROGEN MUSTARD has been used for a variety of clinical diseases that manifest tissue and vascular reactivity, such as rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, periarteritis nodosa, dermatomyositis, and acute and subacute glomerulonephritis.1–9 The action of nitrogen mustard (hereinafter termed HN2) is inhibitory on accelerated growth of normal as well as of neoplastic cells.10 Chemically, HN2 is methyl-bis-(β-chloroethyl)-amine hydrochloride, an alkylating agent that replaces hydrogen with alkyl groups in organic molecules; it contains two reactive ethyleneimine groups10 that inhibit actively growing and proliferating cells.
The basic mechanism of the inhibition is not understood; however, it has been postulated11 that inhibition of enzymatic activity might account for its action, although to inhibit most enzymatic systems in vitro, a far higher concentration of HN2 is needed than is possible to achieve in vivo. A more likely theory12 takes cognizance of the high degree of reactivity of HN2 with specific nucleoproteins that are essential to cellular reproduction. Viruses that are rich in nucleoproteins are highly susceptible to irreversible inactivation by HN2, a susceptibility that appears to be directly related to viral nucleic acids. Viruses that contain largely or exclusively desoxyribonucleic acid are more readily inactivated by HN2 than are those that contain predominantly ribonucleic acid. This selectivity of action suggests that HN2 may act directly on desoxyribonucleic acid and, by interfering with the anabolism of this important nuclear constituent, render the cells nonproliferative.11
After intravenous administration of HN2, development of the Shwartzman phenomenon is suppressed.13,14 Becker15 postulated that the mechanism of . . .