1 The effect of specific antigen challenge on the lung function of eight allergic asthmatic patients after placebo and indomethacin pretreatment has been investigated. 2 Plasma levels of thromboxane B2(TxB2), metabolite of thromboxane A2, 6-ketoPGFia, metabolite of epoprostenol, (prostacyclin, PGI2) and ,-thromboglobulin (,TBG) following antigen challenge in these eight patients have also been measured after placebo and indomethacin pretreatment. 3 Each patient underwent two antigen inhalations 1 week apart. One challenge took place after 4 days pretreatment with indomethacin capsules 25 mg four times daily, and the other took place following 4 days placebo pretreatment, one matched capsule four times daily. The order of administration was random but balanced and blind with respect to the patient. 4 Following placebo pretreatment two patients presented with an early antigen response only, four presented with a biphasic antigen response and two presented with a delayed antigen response only. The asthmatic response for each patient was consistent on reexposure. 5 Indomethacin pretreatment suppressed the delayed antigen induced asthmatic response. This suppression was reproducible. 6 There was a rise in plasma TxB2 levels on antigen challenge following placebo pretreatment but not following indomethacin pretreatment, whereas there was a rise in 6-keto-PGF1I after antigen challenge following indomethacin but not placebo pretreatment.7 No significant change in plasma ,BTBG or platelet counts from control values was observed following antigen challenge with either placebo or indomethacin pretreatment. 8 It is suggested that the production of PGI2 and suppression of TxA2 by indomethacin pretreatment contribute to the suppression of the delayed antigen induced asthmatic response and that platelets play a minimal role in this process.Keywords thromboxane B2 6-keto-prostaglandin Fla P-thromboglobulin platelets indomethacin antigen-induced asthma

The therapeutic potential of non-steroid anti-inflammatory drugs in clinical asthma is offset by the real possibility of hypersensitivity and induction of severe airways obstruction. The influence of indomethacin on the antigen-induced asthmatic response was tested. Early and delayed asthmatic responses were recorded after antigen challenge in 13 subjects. Indomethacin pretreatment totally or partially inhibited the delayed asthmatic response in 10 of 11 subjects. Inhibition by indomethacin of products of the arachidonic cascade which participate in the pathogenesis of the delayed asthmatic response could explain this phenomenon. A similar therapeutic response was documented without adverse drug reactions when five subjects were restudied after several months. In the same group the early asthmatic response was suppressed in six, enhanced in two and unchanged in four of 12-subjects. This variable response indicates that spasmogenic prostaglandin breakdown products may be important for certain individuals, but are generally of less importance in the early asthmatic response. Clinical trials with indomethacin as a steroid saving agent in allergic asthma appear feasible and can be conducted safely.

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