Effect of pretreatment with heparin on pulmonary and cutaneous response

Although anticoagulant properties of glycosaminoglycan heparin are primary in medicine, a variety of other biological functions related to heparin 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 heparin may act as a natural anti-inflammatory molecule and modify these reactions. Therefore, the purpose of the present study was to determine the role of heparin in allergic inflammatory responses: the pulmonary reaction and the cutaneous response, in a double-blind, placebo-controlled, crossover randomized trial. To evaluate the effect of heparin on methacholine-induced bronchoconstriction, nebulized heparin (20,000 units) was administered to 12 asthmatics and nonspecific challenge was performed immediately thereafter. Measurements of Raw and SGaw were obtained before and 1 hr after nebulization of heparin. In 12 other allergic subjects, heparin (25 U/kg) was given intravenously 10 min before skin prick test. We demonstrated that pretreatment with heparin reduced 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 bronchoconstrictor 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 heparin may have a transient inhibitory role in allergic reactions.