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

Abstract

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, noncapsaicinized (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, PGF2 alpha, 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 neurokinin 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.(ABSTRACT TRUNCATED AT 250 WORDS)

GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

“…Though not in every experimental condition (Ingenito et al, 1991), the involvement of capsaicin-sensitive fibres in models of allergy is well established (Saria et al, 1983;Manzini et al, 1987;Alving et al, 1987;Gentilini et al, 1990c;Kohrogi et al, 1991). This was also confirmed under our experimental conditions, where depletion of neuropeptide-containing terminals by superfusion with capsaicin reduced the tracheal strip response to OA.…”

Greater Involvement of Neurokinins Found in Guinea Pig Models of Severe Asthma Compared with Mild Asthma

“…On the other hand, IBR was not significantly inhibited by capsaicin pretreatment in model I and model II animals, indicating that neurokinins were not highly involved in the ovalbumin-induced IBR. These results are consistent with the previous observations that capsaicin pretreatment did not prevent the allergen-induced immediate bronchoconstriction in guinea pigs [32, 33], and that intravenous administration of neurokinin receptor antagonist had no effects on the immediate ovalbumin-induced bronchoconstriction [34]. On the other hand, other reports have shown that capsaicin pretreatment inhibited respiratory system resistance and elastance after antigen inhalation in guinea pigs repeatedly sensitized with ovalbumin aerosol [20], and capsaicin pretreatment resulted in a decreased immediate pulmonary mechanical response to antigen inhalation in sensitized guinea pigs [19].…”

“…On the other hand, capsaicin pretreatment had no effect on eosinophil accumulation in model I animals. This is consistent with the previous observation in which capsaicin pretreatment did not affect increase in BALF cell counts after antigen inhalation in sensitized guinea pigs [32]. We have previously observed that ovalbumin-induced eosinophil accumulation is inhibited by thromboxane synthase inhibitor and platelet-activating factor antagonist in a guinea pig model of mild asthma [46].…”

Involvement of NK2 receptors rather than NK1 receptors in bronchial hyperresponsiveness induced by allergic reaction in guinea‐pigs

“…Although Ingenito et al (1991) andLai, (1991) suggested that tachykinins do not contribute to the bronchoconstriction evoked by antigen challenge in sensitized guinea-pigs, found that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction. The latter group investigated the bronchoconstrictor effect of inhaled ovalbumin (OA) at low and high concentrations after pretreatment with phosphoramidon, NKI and NK2 receptor antagonists in sensitized guinea-pigs in vivo.…”