Histamine releasability after adenosine challenge in subjects with allergic and non-allergic rhinitis: possible implications for mast cell priming

Nasal provocation with adenosine 5'-monophosphate elicits nasal symptoms in subjects with rhinitis. Histamine released from airway mast cells may play a role in adenosine-induced nasal responses. To investigate the possible role of histamine in mediating adenosine-induced nasal responses, we measured its release in the fluid obtained by nasal lavage after adenosine 5'-monophosphate, guanosine 5'-monophosphate, and placebo instillations. Nasal lavages were performed before and 3, 5, 10, 15, 30 and 45 min after challenge with adenosine 5'-monophosphate, guanosine 5'-monophosphate, and normal saline in 11 patients with rhinitis and 7 normal subjects in a double-blind randomized placebo-controlled cross-over study to evaluate symptoms and to monitor changes in histamine levels. No symptoms or significant increases in histamine were observed after guanosine 5'-monophosphate and placebo challenge. Symptom scores increased in response to adenosine 5'-monophosphate challenge in the rhinitic subjects but not in the normal controls. Nasal provocation with adenosine elicited a significant release of histamine in the nasal lavage fluids with an immediate peak response: its median (range) concentration increased from the baseline value of 1.33 (0.16-14.54) ng/mL to 2.68 (0.31-61.11) ng/mL at 3 min. However, increased histamine levels were not associated with nasal symptom scores. When compared to non-atopic subjects, significantly higher levels of histamine were seen in the nasal lavage fluids of the atopic subjects following adenosine challenge. In the atopic subjects, the median (range) histamine concentration increased from the baseline value of 1.54 (0.16-14.54) ng/mL to that of 4.21 (0.70-61.11) ng/mL at 3 min, whereas no increment was seen in the non-atopic subjects, their histamine concentration being 0.81 (0.29-5.56) ng/mL and 0.74 (0.31-14.25) ng/mL at baseline and 3 min after adenosine challenge respectively. These findings indicate that adenosine elicits nasal responses in patients with rhinitis but not in normal controls. Moreover, adenosine elicits an immediate rise in histamine levels in the nasal lavage fluid, with the highest rise in atopic compared to non-atopic volunteers, suggesting that the nasal responses to adenosine may be an index of mast cell priming.