Journal of immunopharmacology最新文献

Patients with the acquired immunodeficiency syndrome (AIDS) are susceptible to a variety of opportunistic pathogens which require intact cellular immunity for control and eradication. We evaluated interleukin 1 and 2 production in 12 homosexual men without AIDS but with evidence of altered cell-mediated immunity and serologic evidence of infection with human T-cell lymphotrophic virus type III (HTLV-III), the etiologic agent of AIDS and found production of both factors diminished compared to heterosexual controls. Therafectin (SM-1213) is a new agent which selectively activates macrophages and stimulated interleukin 1 production in vitro. Therafectin was administered to these same 12 patients in a double-blind, placebo controlled trial. We failed to find any significant changes in their immunologic status including interleukin 1 or 2 production.

Prostaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher X Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGE's than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested.

This study investigated whether in vitro immunotherapy with rIL-2 which augments human natural cytotoxicity and generation of lymphokine-activated killer cells diminished or inhibits the severity of therapeutically induced human in vitro NK immunosuppression. We demonstrate that rIL-2 induces a rapid and potent enhancement of cytolytic killing and that pretreatment of effector cells for one hour with rIL-2 yields effector cells which are more resistant to drug-induced immunosuppression. Additionally, we demonstrate cells pretreated for 24 hours with rIL-2 were less sensitive to drug inhibitory effects than rIL-2 non-treated or one hour pretreated effector cells. Our data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible.

The relationship between enantiomeric homogeneity of three oxazaphosphorine drugs: cyclophosphamide, ifosfamide and trofosfamide and their antitumor activity was evaluated by standard screening tests against four in vivo transplantable tumor models: L 1210 and P 388 lymphoid leukemias, Lewis lung carcinoma and 16/C line of mouse mammary adenocarcinoma. It was shown that the stereodifferentiation of anti-tumor effect of enantiomers was not outstanding although quite consistently in favour of levorotatory forms. The only exception was seen for cyclophosphamide enantiomers tested against leukemias where R/+/form was more effective than S/-/or racemate.

A soluble form of the reticuloendothelial- and immune modulating agent glucan (glucan-F) has been evaluated for its effects on hemopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell numbers (GM-CFC), and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage colony stimulating activity (CSA) were also elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be induced by intravenous administration of particulate glucan (glucan-P). In contrast to glucan-P, however, intravenous glucan-F administration has been shown not to induce granuloma formation and severe hepatosplenomegaly, thus the potential clinical use of glucan-F as a hemopoietic stimulant is more likely than that of glucan-P.

Treatment with the beta blocker acebutolol may trigger antinuclear antibody (ANA) production. We retrospectively studied 97 sera from 47 patients who developed ANA during acebutolol treatment. Anti-histone and anti-denatured (ss) DNA antibodies were found in 53% and 66% respectively of the sera tested. The activities of these two antibodies correlated well with the total ANA titer. Anti-native (ds) DNA were absent or present at low titer. This immunochemical pattern of acebutolol-induced ANA is similar to that reported for other drug-induced ANA. To date, the presence such isolated ANA is not known to expose patients to any particular risk other than exceptional and minor clinical manifestations of lupus which are rapidly reversible following therapy cessation.

Complement components and complement breakdown products have been found to participate in the regulation of the immune response. In the present study we investigated the effect of C3 and its fragments, C3b, C3c and C3d on human allogeneic cell mediated lympholysis (CML). C3 and C3b at a concentration of 275 M X 10(-9) and C3d at a concentration of 330 M X 10(-9) enhanced human allogeneic CML by at least two fold. In contrast C3c did not affect CML responses. Both C3b and C3d had to be present at the initiation of the cultures in order to exert their effect. Similar doses of C3b and C3d did not affect the mixed lymphocyte responses (3H-thymidine uptake) while higher doses were clearly inhibitory. None of the preparations induced proliferative or cytotoxic responses in the absence of allogeneic stimulating cells. C3b and C3d added to the mixed lymphocyte cultures caused increased production of interleukin 2. We conclude that C3b and C3d facilitate allogeneic cytotoxic responses through increased production of interleukin 2.

With repeated administration to animals, the cationic, amphiphilic drug, chlorphentermine (CP), has been shown by others to induce a phospholipidosis in lymphocytes. In the present study mouse splenic lymphocytes, exposed to CP, either in vivo or in vitro, developed morphological changes consistant with the induction of phospholipidosis. In addition, CP induced functional changes in lymphocytes. Mice, treated with CP in vivo, demonstrated a significantly depressed ability to generate a delayed hypersensitivity response or to produce antibody-secreting cells against de novo antigens. Mouse splenic lymphocytes, exposed to 10(-7) M CP for 3 days in vitro, demonstrated a significantly depressed blastogenic response to the mitogens phytohemagglutinin, concanavalin A and lipopolysaccharide. CP inhibited an event that occurred early during lymphocyte activation, but was subsequent to mitogen/receptor coupling. In addition, CP significantly depressed the increased uptake of choline that occurs in lymphocytes following cellular activation. Since the presence of phospholipidosis is indicative of an impairment in phospholipid metabolism, these results taken together provide evidence for a relationship between this phenomenon and altered immune function.