Antigen-provoked Increase in Histamine Reactivity: Observations on Mechanisms

Abstract

Abstract To investigate the effect of antigen provocation on nonspecific reactivity to histamine, nine allergic individuals underwent multiple nasal challenges with histamine or antigen. The response to challenge was assessed by counting the number of sneezes and measuring the levels of albumin and TAME-esterase (TAME; [3H]N-α-tosyl-L-arginine methyl ester) activity in recovered nasal lavages. In the case of antigen, levels of histamine were also measured. In response to histamine, the subjects sneezed and had increased levels of albumin and TAME. The responses to antigen or histamine were unchanged 24 h after histamine provocation. The responses to histamine provocations were increased with respect to symptom scores and to the levels of TAME activity and albumin in nasal lavages compared to baseline challenge, however, 24 h after antigen provocation. Increasing antigen exposure from 1 to 3 days did not further increase the responsiveness to histamine. Histamine reactivity returned to baseline 12 days after antigen exposure. The number of eosinophils, neutrophils, and alcian blue-positive cells in the lavages after antigen challenge and before the histamine challenges correlated with the changes in response to histamine. The increase in sneezing induced by antigen stimulation correlated with the increase in the same parameter after histamine provocation 24 hr after antigen challenge (r = 0.88; p < 0.01). Surprisingly, the other parameters assessed did not show similar correlations. We conclude that (1) histamine provocation does not induce increased reactivity to itself or to antigen, (2) antigen induces a reversible increase in responsiveness to histamine that is associated with an inflammatory cell infiltration, and (3) there is a weak relationship between an antigen-induced increase in specific (antigen) and nonspecific (histamine) reactivity.