Intermittent corticotrophin therapy. Study of lymphocyte transformation in vitro in rheumatoid arthritis.

The assumption that the most effective way to use corticosteroids to suppress disease is to give these agents in divided doses two or three times daily was challenged by Reichling and Kligman (1961) and later by Harter, Reddy, and Thorn (1963). They suggested that alternate day administration could be equally satisfactory, with the advantage that less suppression of the hypothalamic-pituitaryadrenal axis was induced. Grant, Forsham, and DiRaimondo (1965) also found that one daily morning dose produced less adrenal suppression than divided doses. Intermittent treatment with corticotrophin based on a regime of injections of ACTH gel every 48 or 72 hours is also clinically effective (Nelson, Mackay, Sheridan, and Weaver, 1966). The nature of the therapeutic benefit induced by steroids or corticotrophin on cellular or enzymatic activity which persists during the interval between doses is not clear, but it does appear that many individuals with diseases such as rheumatoid arthritis or asthma are benefited for a period longer than the recognized metabolic effects of these drugs. We have administered corticotrophin gel to patients with rheumatoid arthritis and studied lymphocyte transformation in vitro of blood samples obtained at various times after administration of corticotrophin, in an attempt to determine whether changes in lymphocyte activity persist beyond the duration of the induced rise in plasma cortisol.