Lung function and plasma levels of thromboxane B2, 6-ketoprostaglandin F1 alpha and beta-thromboglobulin in antigen-induced asthma before and after indomethacin pretreatment.
The effect of specific antigen challenge on the lung function of eight allergic asthmatic patients after placebo and indomethacin pretreatment has been investigated. Plasma levels of thromboxane B2(TxB2), metabolite of thromboxane A2, 6-keto-PGF1 alpha, metabolite of epoprostenol, (prostacyclin, PGI2) and beta-thromboglobulin (beta TBG) following antigen challenge in these eight patients have also been measured after placebo and indomethacin pretreatment. 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. 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 re-exposure. Indomethacin pretreatment suppressed the delayed antigen induced asthmatic response. This suppression was reproducible. 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-PGF1 alpha after antigen challenge following indomethacin but not placebo pretreatment. No significant change in plasma beta TBG or platelet counts from control values was observed following antigen challenge with either placebo or indomethacin pretreatment. 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.
Shephard
E G
EG
Malan
L
L
Macfarlane
C M
CM
Mouton
W
W
Joubert
J R
JR
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood*; D001609:Beta-Globulins / Q000032:analysis*; D006801:Humans; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000502:physiology*; D008448:Maximal Expiratory Flow Rate; D012129:Respiratory Function Tests; D013929:Thromboxane B2 / Q000097:blood*; D013931:Thromboxanes / Q000097:blood*; D013997:Time Factors; D001620:beta-Thromboglobulin / Q000032:analysis*
D001609:Beta-Globulins; D013931:Thromboxanes; D001620:beta-Thromboglobulin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin