The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.

No abstract

1 Since both histamine and 5-hydroxytryptamine (5-HT) can be released by murine mast cells, we investigated the possible role of these autacoids on airway hyperresponsiveness (AHR), eosinophil in®ltration and serum-IgE levels in a murine model of allergic asthma. 2 Ovalbumin-sensitized mice were exposed to either ovalbumin (2 mg ml 71 ) or saline aerosols on 8 consecutive days. Starting one day before the challenge, animals were injected i.p. twice a day with a 5-HT-type 1 (5-HT 1 ) or type 2 (5-HT 2 ) receptor antagonist (methiotepine, 1.25 or 2.0 mg kg 71 and ketanserin, 12 mg kg 71 , respectively) or a histamine-type 1 (H 1 ) or type 2 (H 2 ) receptor antagonist (mepyramine, 12 or 20 mg kg 71 and cimetidine, 10 or 25 mg kg 71 , respectively). Furthermore, animals were injected with a combination of cimetidine and ketanserin or with an a-adrenoceptor antagonist (phentolamine, 5 mg kg 71 ). 3 In vehicle-treated ovalbumin-challenged animals airway responsiveness to intravenous injections of methacholine in vivo was signi®cantly (9 fold increase, P50.01) increased when compared to vehicletreated saline-challenged animals. Furthermore, ovalbumin challenge of vehicle-treated animals induced a signi®cant increase in both eosinophil numbers in bronchoalveolar lavage (BAL)¯uid (0+0, vehicle/ saline and 15.0+5.9610 4 cells vehicle/ovalbumin, P50.05) and ovalbumin-speci®c IgE levels in serum (157+69 and 617+171 units ml 71, respectively, P50.05) compared to saline-challenged mice. Virtually no eosinophils could be detected in saline-challenged animals after all dierent treatments. 4 Treatment with ketanserin or cimetidine resulted in a partial but signi®cant decrease of the ovalbumin-induced AHR compared to ovalbumin-challenged controls (P50.05) and reduced eosinophil in®ltration after ovalbumin challenge by 60% and 58%, respectively. The combination of cimetidine and ketanserin almost completely abolished AHR whereas eosinophilia was decreased by 49%. No eects of these antagonists were observed on IL-16 levels in BAL¯uid or on serum antigen-speci®c IgE levels. Treatment with either the H 1 -receptor, the 5-HT 1 -receptor or the a-adrenoceptor antagonist, did not decrease the observed ovalbumin-induced airway responsiveness or eosinophilia in vehicle-treated animals. Higher doses of either methiotepine (2.0 mg kg 71 ) or mepyramine (20 mg kg 71 ) did decrease ovalbumin-induced eosinophil in®ltration (by 67%, P50.05 and 73%, respectively), whereas no eects of these antagonists were observed on ovalbumin-speci®c IgE levels in serum. 5 From these data it can be concluded that both histamine and 5-HT play a role in antigen-induced AHR and eosinophilia in the mouse.

Epithelium-derived Fas ligand is believed to modulate inflammation within various tissues. In this paper, we report findings that suggest a similar immunoregulatory role for Fas ligand in the lung. First, Fas ligand was localized to nonciliated, cuboidal airway epithelial cells (Clara cells) throughout the airways in the normal murine lung by employing nonisotopic in situ hybridization and immunohistochemistry. Second, gldmutant mice, which express a dysfunctional Fas ligand protein, were noted to develop prominent infiltration of inflammatory cells in submucosal and peribronchial regions of the upper and lower airways. Third, during allergic airway inflammation induced by ovalbumin in mice, cell-associated staining for Fas ligand mRNA and protein was markedly reduced in the airway epithelium. These data suggest that Clara cell-derived Fas ligand may control immune activity in the airway; thus alterations in this protective mechanism may be involved in the pathogenesis of certain inflammatory conditions of the airway, such as asthma.

It can be concluded that IL-16 has potent immunosuppressive effects on a Th2dominated allergic airway response.