Delayed Hypersensitivity to Tuberculin in Rats: Effects of Antirheumatic Drugs

Abstract

Absfract:The effects of different antirheumatic drugs administered according to various dosing regimes on tuberculin hypersensitivity in rats have been assessed quantitating the changes of exudate volume and mononuclear cells immigration at the site of challenge. Dosing at the time of sensitization with aurothiomalate and D-penicillamine enhanced the cell immigration which was decreased by similar treatment with levamisole. Cyclophosphamide increased the exudate formation. Indomethacin had no effect. Dosing at the time of challenge caused a marked reduction of both the parameters by aurothiomalate and cyclophosphamide and enhancement by levamisole. D-penicillamine increased only the cellular immigration and indomethacin the exudate formation. Long treatment with aurothiomalate and cyclophosphamide suppressed the responses. Similar treatment with D-penicillamine and levamisole produced a significant enhancement. Indomethacin had no effect. The relevance of these findings to the testing and mode of action of antirheumatic drugs is discussed.

Hormesis is central to toxicology, pharmacology and risk assessment

“…While a detailed assessment of hormetic responses of the immune system suggested that most would be beneficial, in about 20% of the cases, the low dose stimulatory response could lead to harmful effects, such as certain autoimmune responses including lupus 75 and tuberculin hypersensitivity. 76 Hormesis in drug discovery, development and in the clinical trial Drug discovery, development and clinical trial efficiency could be significantly enhanced if they were guided by principles derived from an understanding of the concept of hormesis. This is the case for drugs designed to kill harmful agents.…”