Effects of Capsaicin on Mechanical, Cellular, and Mediator Responses to Antigen in Sensitized Guinea Pigs

To assess the role of tachykinins (TKs) in immediate hypersensitivity allergic reactions in guinea pigs (GPs), we compared airway mechanics and bronchoalveolar lavage (BAL) cell and inflammatory mediator profiles in three groups of GPs after ovalbumin aerosol challenge: (1) saline-sensitized, noncapsaicinized (control) (n = 9); (2) ovalbumin-sensitized, noncapsaicinlzed (OS) (n = 9); (3) ovalbumin-sensitized capsaicinized (OSC) (n = 9). Lung resistance (Rl), dynamic elastance (El), BAL cell counts, histamine, and eicosanoid mediator levels were measured at baseline on Day 1, and then on Day 14 after aerosolized antigen challenge. We found significant increases on Day 14 compared with Day 1 in the following: (1) postchallenge Rl and El in OS and OSC GPs, but not in control GPs; (2) BAL total cells and red cells in OS and OSC GPs; (3) BAL prostaglandin D2 (PGD2) thromboxane B2 (TxB2), sulfidopeptide leukotrienes (LTC4/D4/E4), and histamine in OS and OSC animals. Further, when data from all GPs were considered in distributed fashion, we noted positive linear correlations between peak postchallenge Rl versus BAL concentrations of each of the following: PGD2, PGF2α, TxB2, LTC4/D4/E4, leukotriene B4 (LTB4), and histamine. We found no significant differences in mediator or cellular responses between OS and OSC GPs. To verify that our method of capsaicinization resulted in TK depletion from the lungs of OSC GPs, substance P (SP) and neuroklnin A (NKA) lung tissue levels were measured by ELISA in seven other animals, four treated with capsaicin using the same protocol and three treated with diluent. Ninety and 91% reductions in tissue levels of SP and NKA were observed, respectively, in capsaicin-treated GPs, compared with that in control animals. We conclude that: (1) multiple mediators are present in BAL fluid after antigen challenge in the Intact, sensitized GP; (2) BAL levels of PGD2, PGF2α, LTC4/D4/E4, TxB2, LTB4, and histamine correlate significantly with the observed increases in Rl; (3) no differences exist between OS and OSC animals in mechanical, cellula or mediator responses to antigen challenge, suggesting that acute antigen-induced bronchoconstriction in GPs occurs even when lung TK levels are greatly reduced.