Category Archives: Theophylline

Asthmatic patients appear to have more viral respiratory infections than do normal subjects, and those respiratory infections may trigger the exacerbations of asthma. Thus, there is a possibility that the inhibition of NK cell activity, one of the primary defense mechanisms, may induce more frequent infections and asthmatic attacks. (more…)

In this study, we demonstrated that theophylline could inhibit NK cell activity in vivo. It should be noted that the concentration of theophylline that yielded the same amount of inhibition was lower in vivo than by direct addition in vitro. We suggested that long-term incubation causes strong suppression of the activities of individual NK cells, even at low concentrations of theophylline in vivo. (more…)

The amount of inhibition of NK cell activity observed in vivo was about 40 percent, which was about equal to that observed by direct addition in vitro at the concentration of 1X 10_4M aminophylline (2 X 10'M theophylline). The NK cell activity was returned to the level of before administration on the seventh day after cessation of administration (Fig 2A). (more…)

NK CeU Activity Inhibited by Orally Administered Theophylline The direct addition of more than 5x 10 aminophylline significantly inhibited NK cell activity in vitro. Since aminophylline contains two molecules of theophylline per one molecule, this is the maximum therapeutic concentration. Furthermore, NK cell activity of preincubated PBLs was also inhibited. Those in vitro effects suggested that theophylline may inhibit the NK cell activity at therapeutic concentrations (5iig/ml to 20iig/ml; 2.2 to llxl0_5M) in vivo. To test this possibility, we administered sustained-release theophylline to five healthy volunteers. The protocol is described in the methods section. As shown in Figure 2A, NK cell activity was significantly decreased compared to that before administration (p<0.01). (more…)

Direct Addition of Aminophylline to Effector-Target CeU Cultures in Vitro The direct addition of concentrations of aminophyl-line that exceeded 5 X 10 “M inhibited NK cell activity in a dose-dependent manner. Representative data obtained from three independent experiments on one individual are shown in Table 1. The degree of inhibition was similar in two other individuals, and the inhibitory effect occurred at various effector-target ratios (data not shown). Fifty percent inhibition was achieved at between 1 and 5x 10_4M. The inhibition was not due to direct cytotoxicity of this compound because the viability of PBLs after incubation with aminophylline (1 x 10~M) for 4 h was greater than 95 percent of untreated control PBLs. Although aminophylline contains ethylenediamine, this compound could not inhibit NK cell activity even at 1 x 10-3M (data not shown). (more…)

Theophylline For in vitro experiments, aminophylline (theophylline ethylene-diamine [Sigma Chemical Co.] or ethylenediamine [Wako Chemicals]) was diluted in complete medium to give the final molar concentrations as indicated. In the preincubation studies, effector cells were incubated with 10_3M aminophylline for 30, 60, 120, or 180 minutes and then washed extensively before the assay. For in vivo experiments, one sustained-release theophylline tablets (Theo-Dur; 200 mg and 100 mg) was used. (more…)

Cells Peripheral blood mononuclear cells were separated from heparin-ized normal human blood by Ficoll-Conray density-gradient centrifugation and were washed and resuspended in RPMI 1640 medium supplemented with 10 percent heat-inactivated fetal bovine serum (GIBCO), 2 mM L-glutamine, and gentamicin (60ngfail) (complete medium). The PBMCs were then depleted of adherent cells by plastic adherence as described previously. The remaining cells, referred to hereafter as PBLs, were washed and resuspended in complete medium. The viability of cells was assessed by the trypan blue dye exclusion test. (more…)

Theophylline has been used frequently in the treatment of patients with bronchial asthma and chronic obstructive pulmonary disease. The appearance of oral sustained-release products facilitated the regular use for maintenance of more stable therapeutic concentrations. It is well known that theophylline has a wide variety of side effects, including symptoms of the gastrointestinal and central nervous systems. These symptoms occur relatively early after initiation of medication. On the other hand, there are some reports that indicate potentially immunosuppressive aspects of this drug. Thus, long-term observation for ruling out of such side effects should be needed. (more…)