Suppressive effects of IPD-1151T (suplatast-tosilate) on induction of mast cells from normal mouse splenocytes.

The influence of IPD-1151T (suplatast-tosilate) on murine mast cell induction was examined by in vitro cell culture. Splenocytes from BALB/c mice suspended in RPMI-1640 medium supplemented with interleukin-3 were cultured in the presence or absence of IPD-1151T. Half of the total volume of the medium was changed every 4-5 days. The number of mast cells increased with culture time and reached a peak on the 16th day when the cells were cultured without IPD-1151T. However, the growth of mast cells from the splenocyte culture was dose dependently inhibited by IPD-1151T. Furthermore, IPD-1151T inhibited the proliferation of mast cell progenitor cells, IC-2, but not that of splenocytes or mature mast cells.

[Analysis of differential cell counts of sputa induced by inhalation of ultrasonically nebulized hypertonic saline or distilled water in asthmatic patients].

Bronchial asthma is an inflammatory disease of the airways, and a simple method of evaluating inflammation, safer than BALF or bronchial mucosal biopsy, has long been sought after. The induction of sputa by the inhalation of an appropriate solution and the examination of the induced sputa may provide such a method. We compared the safety of two sputum induction methods, ultrasonically nebulized hypertonic saline inhalation and distilled water inhalation, and examined the usefulness of differential cell counts of the induced sputa. The safety of these methods was ascertained by determining lung functions (FEV1.0, PEFR) and urinary leukotriene E4 before and after inhalation of these solutions, and the usefulness of differential cell counts of induced sputa by examining the uniformity/reproducibility. Only after the inhalation of distilled water did the lung function reveal a statistically significant decrease when the data were compared with the control values for each of the two methods (p < 0.01), and when the data obtained with distilled water inhalation and hypertonic saline inhalation were compared (p < 0.05). The urinary leukotriene E4 levels obtained were not very different between the two methods; however, in two patients, urinary leukotriene E4 levels were increased markedly only after inhalation of distilled water. The uniformity of the sputum differential cell counts in the same specimen (evaluated by intraclass correlation coefficient) and inter-specimens (evaluated by Friedman test) was satisfactory for both methods, except for basophils. Hypertonic saline inhalation at 24-hour intervals gave a better reproducibility in differential cell counts of the induced sputa (evaluated by interclass correlation coefficient), when compared with distilled water inhalation. These results suggest that hypertonic saline inhalation is safer and more useful than distilled water inhalation for induction of sputum in a uniform and reproducible way, and that the induction of sputum by hypertonic saline inhalation will be clinically useful in asthmatic patients who cannot expectorate sputa spontaneously.

[Effect of indomethacin on the release of chemical mediators from human peripheral leukocytes].

We studied the effect of indomethacin (IND) on the release of chemical mediators from human peripheral leukocytes and the relation of prostaglandin (PG) E2 and PGI2 to that effect. We stimulated the leukocyte suspensions with calcium ionophore A23187 (CaI, 10(-6) M) accompanied with IND (10(-5) M), PGE2 (10(-5) M) or PGI2 (10(-5) M) and measured the levels in histamine (HA), leukotriene C4/D4/E4 (peptide-LTs) and LTB4 in the supernatant fluid. The increase of HA levels induced by CaI was significantly enhanced by IND (p < 0.01), and the enhancement was significantly inhibited by PGE2 (p < 0.05) and PGI2 (p < 0.01). The release of peptide-LTs was not enhanced by IND and was inhibited significantly by PGE2 (p < 0.05) and PGI2 (p < 0.01). IND did not affect the release of LTB4 induced by CaI. However, LTB4 release was also significantly inhibited by PGE2 and PGI2 (p < 0.01). These results suggest that the inhibitory effect of IND on the production of PGE2 and PGI2 results in the enhancement of HA release. PGE2 and PGI2 have a potent inhibitory effect on the release of HA, peptide-LTs and LTB4 from human leukocytes.

Change in responsiveness of airway and beta-adrenoceptor in guinea pigs.

Allergen inhalation challenge resulted in significant (p < 0.05) increase in airway responsiveness to methacholine soon after immediate airway response (IAR) in guinea pigs actively sensitized with inhaled ovalbumin (OA) in vivo. We have investigated the involvement of thromboxane (Tx) A2 and platelet activating factor (PAF) in this airway hyperresponsiveness (AH). Pretreatment with CS-518, a selective thromboxane synthetase inhibitor, significantly inhibited both IAR (p < 0.07) and AH (p < 0.01), while pretreatment with WEB 2086, a PAF receptor antagonist, significantly inhibited only IAR (p < 0.05), but not AH after IAR. Propranolol, when inhaled before OA exposure, had no effect on bronchomotor tone, but if inhaled after IAR, it caused immediate death of guinea pigs. This result suggests that hyperresponsiveness of beta-adrenoceptor to propranolol may be induced by IAR. Examination of bronchoalveolar lavage (BAL) fluid revealed that no changes in cellular content were observed 60 min after OA exposure. In vitro, responsiveness of tracheal smooth muscle to carbachol was not changed by sensitization. Furthermore, anaphylactic reaction in vitro had no effect on the responsiveness. We conclude that airway responsiveness increases soon after IAR when infiltration of inflammatory cells is not yet found in vivo. It is also suggested that TxA2 but not PAF is involved in AH. Hyperresponsiveness to propranolol after IAR in OA sensitized guinea pigs illustrates the possibility of changes in function of beta-adrenoceptor after IAR.