EFFECT OF PRETREATMENT WITH HEPARIN ON PULMONARY AND CUTANEOUS RESPONSE

Although anticoagulant properties of glycosaminoglycan heparin are pri mary in medicine, a variety of other biological functions related to h eparin have been suggested. Since heparin is a selective inhibitor of inositol triphosphate (IP3) receptors that are involved in release of calcium in mast cells and many other cells, it is possible that hepari n may act as a natural anti-inflammatory molecule and modify these rea ctions. Therefore, the purpose of the present study was to determine t he role of heparin in allergic inflammatory responses: the pulmonary r eaction and the cutaneous response, in a double-blind, placebo-control led, crossover randomized trial. To evaluate the effect of heparin on methacholine-induced bronchoconstriction, nebulized heparin (20,000 un its) was administered to 12 asthmatics and nonspecific challenge was p erformed immediately thereafter. Measurements of Raw and SGaw were obt ained before and 1 hr after nebulization of heparin. In 12 other aller gic subjects, heparin (25 U/kg) was given intravenously 10 min before skin prick test. We demonstrated that pretreatment with heparin reduce d skin test reactivity from 24.06 +/- 1.2 mm to 18.26 +/- 2.27 mm and increased the methacholine PC20 value from 1.69 +/- 0.48 mg/ml to 8.14 +/- 3.11 mg/ml (p < 0.05), but did not prevent an increase in Raw and /or a decrease in SGaw. Heparin modified the methacholine-induced bron choconstrictor response, but this did not reflect a protective effect in airway resistance and specific conductance. These data suggest that anti-inflammatory effects of heparin are time-dependent and/or that h eparin may have a transient inhibitory role in allergic reactions.