SUMMARYMechanisms regulating the balance of T-helper 1 ( Th1) and T-helper 2 ( Th2) immune responses are of great interest as they may determine the outcome of allergic and infectious diseases. Recently, in mice, nitric oxide ( NO), a powerful modulator of inflammation, has been reported to preferentially down-regulate Th1-mediated immune responses. In the present study, we investigated the effect of NO on the production of Th1-and Th2-associated cytokines by activated human T cells and human T-cell clones. Cytokine secretion was measured in the presence of the NO-donating agents 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). Both NO-donors markedly inhibited the release of interferon-c (IFN-c), interleukin-2 (IL-2 ), IL-5, IL-10 and IL-4 by anti-CD3 activated T cells. A preferential inhibition of Th1-associated cytokines was not observed. Neither was nitrite found in the supernatants of activated T cells, nor was specific mRNA for inducible and constitutive NO synthase detectable, indicating that T cells themselves did not contribute to the observed effect of the NO donors. Costimulation with anti-CD28 monoclonal antibodies (mAb) prevented SIN-1/SNAP-mediated down-regulation of cytokine production only in part. In contrast, when T cells were stimulated by phorbol-ester and ionomycin, they were refractory to SIN-1-induced inhibition of cytokine production. When SIN-1 was added after the onset of anti-CD3 stimulation, the inhibitory effect was found to be less pronounced, indicating that SIN-1 may interfere with early signal transduction events. The addition of superoxide dismutase (SOD) and catalase did not restore the effects of SIN-1, demonstrating that the inhibition of cytokines was due to NO and not to oxygen intermediates. Furthermore, 8-Br-cGMP-mediated increase of intracellular cGMP caused the same pattern of cytokine inhibition as observed with SIN-1 and SNAP. Using a single cell assay, these agents were shown to reduce the frequency of IFN-c-producing T cells, suggesting that not all T cells are susceptible to SIN-1/SNAP. However, cytokine production by purified T-cell subpopulations (CD4+, CD8+, CD45RA+, and CD45RO+) was equally impaired by NO donors. In conclusion, in contrast to the murine system, our results do not provide evidence that NO preferentially inhibits Th1-cytokine secretion of activated human T cells in vitro.

A multicenter randomized 4-week interindividual double-blind study was carried out in 58 hospitalized patients with major depressive disorder (DSM III 296.23,296.22,296.33,296.32,296.53 and 296.52) to test the dose-effect relationship of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram: 3 × 0.25 mg, 3 × 0.50 mg and 3 × 1.00 mg rolipram/day. With respect to the desired effect, the 3 × 0.50 mg dosage stood out from the others in almost all relevant parameters. With respect to the response rate, the efficacy of the 3 × 0.25 mg dosage was about the same as that reported in the literature for placebo. The inferior performance of the 3 × 1.00 mg dosage compared to the 3 × 0.50 mg dosage might indicate a reverse U-shaped dose-effect relationship. There was good tolerance to all three dosages. There were no findings that might cast doubt on the safety of the dosages tested.

In a first operative stage, 4 dogs were prepared with Heidenhain pouches (HP) and 3 with Pavlov pouches (PP), 2 of the latter with an additional esophageal cannula. In a second stage all dogs had a selective proximal vagotomy (SPV), and in a third stage a submucosal pyloroplasty (P). Sham feeding experiments were carried out on the 2 dogs with PP and an esophageal fistula before and after SPV. Feeding tests were performed in all animals after the three operative procedures. Gastrin release after sham feeding increased significantly after SPV, whereas PP acid secretion was abolished. Gastrin release after feeding increased significantly after SPV in both HP and PP dogs. Acid secretion from HP was correlated with the changes in postprandial serum gastrin levels. PP acid secretion was diminished after SPV, in spite of the elevated gastrin levels. Subsequent pyloroplasty induced a significant decrease in the postprandial gastrin levels in both HP and PP dogs. However, acid secretion decreased significantly only in HP dogs.

The measurement of prostaglandin E₂ (PGE₂) concentrations in the serum and prostatic fluid of healthy men, patients with prostatic hyperplasia and of patients with prostatitis was attempted and correlated to the state of disease, respectively. PGE₂-concentrations with prostatic fluid of healthy men were found to be significantly lower than in patients with prostatitis. Corresponding to the course of treatment concentrations normalized, being favorably influenced by sitosterin as an adjuvant medication. Compared to healthy men, PGE₂ concentrations in the prostatic fluid of patients with hyperplasia of the prostate incline to lower levels.