Nasal response to a single antigen challenge in patients with allergic rhinitis — inflammatory cell recruitment persists up to 48 hours

BACKGROUND: Allergen challenge in some patients with respiratory allergy is followed by an early and a late reaction. OBJECTIVE: To evaluate the duration of mediator release and inflammatory cell recruitment during the late antigen-induced nasal response. METHODS: Eight patients with seasonal allergic rhinitis due to grass pollen underwent local challenge with the relevant allergen, a non-relevant allergen (Parietaria judaica), and nebulized saline solution. Nasal lavages were performed at baseline and 6, 24, 48, 72 h after challenge. Eosinophil cationic protein (ECP), leukotriene C4 (LTC4), leukotriene B4 (LTB4) myeloperoxidase (MPO) and prostaglandin D2 (PGD2) levels were radioimmunoassayed and histamine concentration was measured by an automated fluorometric method. RESULTS: Nasal challenge with the relevant antigen induced a response 6 h after stimulation, which subsided within 24 h. Eosinophilia, observed in the nasal lavages collected from 6 to 24 h after this challenge, was accompanied by ECP release. Neutrophilia were found in the nasal lavages collected from 6 to 24 h after challenge. The increase in neutrophil number correlated with MPO levels and LTB4 concentrations, but not with the intensity of nasal obstruction. Antigen challenge also induced significant recruitment of mononuclear cells 48 h after provocation. The challenge significantly raised histamine, but not PGD2, levels in the nasal lavages collected 6 h after provocation. A trend towards an increase in LTC4 levels in the nasal lavages collected 6 h after specific antigen challenge was also found. Nasal challenge with a non-relevant allergen or with saline solution did not cause either inflammatory cell recruitment or mediator release. CONCLUSION: Nasal challenge with the relevant antigen can induce a late response characterized by local accumulation of eosinophils, neutrophils and mononuclear cells persisting for 48 h and accompanied by release of ECP, MPO, LTB4 and histamine. These results indicate that a single antigen challenge in patients with allergic rhinitis causes prolonged inflammatory alterations which may contribute to the development of airway hyperreactivity.     

Antiallergic activity of loratadine: inhibition of leukotriene C4 release from human leucocytes

The H₁ antagonist loratadine has the capacity to inhibit histamine release from human basophils. The aim of this study was to investigate whether loratadine can also inhibit leukotriene C₄ (LTC₄) release from human leucocytes. Basophil-enriched mononuclear cell suspensions were prepared by centrifugation of peripheral venous blood (n= 10) on discontinuous Percoll gradients. Leucocytes were stimulated with anti-IgE, N-formylmethionyl-leucyl-phenylalanine (FMLP) and Ca²⁺ ionophore A23187; immunoreactive (i) LTC₄ release in the cell supernatant was measured by a competitive radioimmunoassay and histamine release was evaluated by an automated fluorometric technique. Loratadine, in the concentration range of 1–50μM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine and iLTC₄ release. The concentrations inhibiting 50% of histamine release were 30 μM (anti-IgE), 27μM (FMLP) and 19μM (Ca²⁺ ionophore A23187). The concentrations inhibiting 50% of iLTC₄ release were 2–3 μM (anti-IgE). 11 μM (FMLP) and 1.7μM (Ca²⁺ ionophore A23187). The inhibitory activity on iLTC₄ release was optimal after preincubation for 2h at 37°C, and was no longer evident when leucocytes were stimulated 2h after cell washing. Increased extracellular Ca²⁺ concentrations reduced the inhibitory activity of loratadine. These results indicate that loratadine has the capacity to inhibit the release of preformed and newly generated mediators from human basophil-enriched mononuclear cell suspensions.     

Study of the effects of paf-acether on human nasal airways

In 6 normal subjects and 6 patients with allergic rhinitis, nasal response to insufflation of paf-acether (paf, platelet-activating factor), lyso-paf and histamine was evaluated. Nasal challenge with paf, at doses of 300 and 600 nM, induced nasal obstruction, associated with an increase in nasal airway resistances, measured by anterior passive rhinomanometry. Maximum increase in nasal airway resistance was observed at 30 min after challenge (mean percent change + 481 with 600 nM paf; P less than 0.05). Other symptoms induced by paf insufflation were rhinorrhea (6 out of 12 subjects), itching (8 out of 12), sneezing (4 out of 12) and a burning sensation (6 out of 12). No differences were observed between normal and rhinitic subjects, concerning nasal sensitivity to paf. Neither nasal symptoms nor changes in nasal airway resistance were observed after nasal challenge with lyso-paf (300 and 600 nM); by contrast, histamine (100 nM) induced sneezing, nasal obstruction, itching and rhinorrhea in all the studied subjects, associated with an increase in nasal airway resistance (maximum 5 min after challenge; percent change + 358; P less than 0.02). Nasal effects of paf were not mediated by histamine, since no increase in histamine levels was observed in nasal washings following paf insufflation. We conclude that paf may have pathogenetic relevance in allergic rhinitis.     

LHRH TEST IN BARTTER'S SYNDROME BEFORE AND DURING TREATMENT WITH PROSTAGLANDIN SYNTHESIS INHIBITORS

LHRH tests were performed in two children with Bartter's syndrome before and during treatment with prostaglandin synthesis inhibitors. Before treatment, in patient 1 both basal and peak FSH and LH levels were elevated; in patient 2 basal and peak FSH levels were above the normal range, while basal and peak LH levels were normal. During treatment with an inhibitor of prostaglandin synthesis, abnormal values decreased into the normal range. These results support a possible role of endogenous prostaglandins in regulating gonadotrophin secretion in humans.