Journal of immunopharmacology最新文献

The effect of yeast beta-1, 3-glucan as an immunopotentiator of delayed type-hypersensitivity reactions (DHR) was studied. Delayed-type-hypersensitivity reactions in mice sensitized intraperitoneally (IP) with sheep red blood cells (SRBC) and pretreated three days previously with glucan given IP were significantly increased. However, mice sensitized IP with SRBC three days after the subcutaneous (SC) administration of glucan showed depressed DHR. Glucan given at the same site but not at distance strongly potentiated the DHR induced by SC sensitization with SRBC. Subcutaneous injection of glucan and SRBC given together also resulted in a sustained DHR which persisted twelve days after sensitization when DHR of control mice had waned.

The total complement (CH50) and its fractions C3 and C4 have been assayed for up to two years after surgery in subjects with breast, gastric and colon-rectum carcinomas. In all three types of pathology a constant pattern has been observed. Before surgery the CH50 stayed below the normal range but was increased following surgery. After a month it was again within the normal range and subsequently, according to the clinical evolution of the disease, it remained normal in those patients without relapse or any apparent metastasis, whereas in those patients who displayed metastasis and/or approached the terminal phase it fell below the normal range. The C3 fraction followed the CH50 pattern whereas the C4 did not show any variation correlated with the stages of the disease.

The effects of pyrethroids on the membrane lipid packing order of murine splenic lymphocytes have been investigated by utilizing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Fluorescence anisotropy and lifetime measurements indicated alterations in the environment of the probe at pyrethroid concentrations near 1 microM. Decreased packing order of membrane lipids was detected for permethrin and cypermethrin by decreased anisotropy values. Permethrin and cypermethrin decreased fluorescence lifetime over a concentration range similar to that causing anisotropy changes. Anisotropy was predominantly increased in the presence of fluvalinate and fenpropathrin, indicating pronounced quenching of fluorescence by these compounds. However, the anisotropy changes in response to fluvalinate and fenpropathrin occurred at concentrations which were similar to effective concentrations of permethrin and cypermethrin. Compared to the other pyrethroids tested, allethrin required approximately 10 fold higher concentrations to alter anisotropy and lifetime values. Effects of pyrethroids on the phase transition of dipalmitoyl phosphatidylcholine liposomes were also studied to give further insight into the membrane interactions of these compounds. Results from the liposomal system indicate that the effects of pyrethroids on membrane order which were observed in the lymphocyte may be generalizable to other cell types.

Some potent phosphodiesterase (PDE)-inhibiting dipyridamole derivatives are able to increase the primary immune response in mice immunized with sheep red blood cells (SRBC). 10mg/kg/day of the most potent substance administered in the drinking water increased the number of plaque forming cells (PFC) in spleens of these mice by a factor of about 2 when the treatment was started after immunization. Pretreating the animals did not result in an enhancement of numbers of plaque forming cells. There was no increase in the background number of PFC.

The possible mode of action of Etodolac, a potent anti-inflammatory drug, has been investigated. The effect of Etodolac on macrophage inflammatory depressed the influx of inflammatory macrophages into peritoneal cavity following stimulation with a sterile irritant. This decrease in macrophage accumulation in vivo correlated with the effect of Etodolac on the macrophage chemotaxis in vitro. Etodolac was also capable of reducing the macrophage ability to migrate towards a chemoattractant. In vivo Etodolac should reduce the amount of damage produced at the site of chronic inflammation since fewer macrophages would migrate to the inflammatory sites.

Granulocytosis is a common feature in patients undergoing lithium therapy. With increasing evidence that T lymphocytes play a role in the control of granulopoiesis, we have investigated the effect of lithium administration on circulating levels of T helper and T suppressor cells, as identified by monoclonal antibodies, to determine whether lithium-induced granulocytosis is mediated through changes in peripheral blood T cell subsets. Lithium carbonate was administered to 10 subjects over a 2 week period. Differential leucocyte counts and T, B, T helper and T suppressor lymphocyte enumerations were performed prior to administration of lithium (Day 1) and on 2 occasions (Day 7 and 14) during ingestion of the drug. Ten healthy control subjects were similarly investigated. Small, but significant elevation (p less than 0.05) in neutrophil counts at 7 and 14 days were observed in subjects taking lithium, serum lithium levels at these times were 0.56 +/- 0.27 and 0.68 +/- 0.17 mmol/l, respectively; lymphocyte and monocyte levels were unaffected. The percentages and absolute numbers of circulating T, B, T helper and T suppressor lymphocytes were not significantly altered (p greater than 0.05) during lithium administration and did not differ significantly (p greater than 0.05) from those recorded for the control group. We were thus unable to demonstrate that short-term lithium administration induced changes in the circulating levels of T helper (OKT4+) or T suppressor (OKT8+) cells.

The relationship between the conversion of arachidonic acid (AA) to E series prostaglandins (PGE), indomethacin-sensitive immunoregulation and lymphocyte PGE sensitivity was investigated in the peripheral blood mononuclear cells (PBMC) of normal subjects and disseminated solid tumor patients. Production of PGE was assessed by thin layer chromatography of ether-extracted glass adherent cells following a 24-hour pulse with 3H-AA. Immunoregulatory cell function was assessed in PHA-stimulated PBMC cultured in the presence of the prostaglandin synthetase inhibitor, indomethacin. Lymphocyte PGE sensitivity was assessed in PHA stimulated glass nonadherent cells cultured in the presence of 10(-8) M PGE. The cells from cancer patients demonstrated greater AA conversion to PGE and greater indomethacin sensitive immunoregulatory cell function than the cells of normal subjects. However, lymphocyte PGE sensitivity was comparable for both groups. When levels of arachidonic acid conversion to PGE were correlated to levels of indomethacin-sensitive immunoregulatory cell function by linear regression analysis, a significant correlation was found. These data suggest that the increased indomethacin-sensitive immunoregulatory cell function seen in PBMC from cancer patients can be directly correlated with increased production of E series prostaglandins by cancer patient peripheral blood monocytes.

The substances D-penicillamine, auranofin, chloroquine, levamisole, BM 41.332, azimexone, bestatin, methisoprinol (inosiplex), thymosine (fraction 5), indomethacin and cyclophosphamide were examined comparatively in the delayed type hypersensitivity test after oxazolone sensitisation in mice. It was found, that only the basal antirheumatic drugs D-penicillamine, auranofin, chloroquine and levamisole and also BM 41.332 led to a potentiation of the DTH reactions. Methisoprinol, bestatin, azimexone, thymosine fraction 5 and indomethacin had no effect on the DTH, whilst the immunosuppressant cyclophosphamide led to an inhibition of the DTH reaction. It is concluded that this pharmacological model is suitable for screening of new basal drugs for rheumatoid arthritis.

Recent studies showed that lead acetate has an important immunotoxicity for the phagocytic activity as well as humoral and cell-mediated immunity. We studied the influence of lead acetate on immediate and delayed hypersensitivity. The lead acetate exerts an important action on hypersensitivity reactions whether on rat mast cells degranulation (immediate hypersensitivity) or on contact hypersensitivity.

CCA and D-penicillamine enhanced the NK activity of human lymphocytes in vitro incubation. ADCC activity of the lymphocytes was increased slightly by D-penicillamine but not by CCA. CCA enhanced interferon production from lymphocytes but D-penicillamine did not.