Immunological and non-immunological mechanisms of some of the desirable and undesirable effects of anti-inflammatory and analgesic drugs

Studies were carried out on patients with adverse reactions to aspirin, paracetamol, phenacetin, codeine, dihydrocodeine, some pyrazolone derivatives, and indomethacin. Three clinico-pathological forms of adverse reactions received particular attention: (1) Asthma, with or without manifestations of systemic anaphylaxis; (2) Serum-sickness-like syndrome; (3) Lymph node enlargement with histological features simulating lymphoma or Hodgkin's disease, which occurred in patients receiving phenylbutazone in particular. A variety of immunological investigations, including some in vitro correlates of immediate- or delayed-type allergy, were carried out. The three syndromes seemed to be associated with immediate-type (or immediate-type-like), immediate-type plus delayed-type, and delayed-type allergy, respectively. In most of the patients with immediate-type-like reactions, and where immunological mechanisms were apparently not involved, pharmacological mediators, particularly histamine, were released from their leucocytes when challenged in vitro with the causative agent(s). This suggested that the main underlying abnormality of their asthma or peripheral vascular manifestations was a direct release of mediators by the drugs, i.e. some type of idiosyncrasy. The causative mechanism of this abnormality has not been established yet.