The effect of recombinant interleukin-2 on the course of experimental staphylococcal peritonitis in mice]

The effect of RIL-2 on the survival of mice with S. aureus--induced peritonitis was studied. Animals received bacterial suspension and RIL-2 as following: bacteria--on days 0, +2, RIL-2--day 0 (group 1); bacteria--days 0, +4, RIL-2--days 0, +2 (group 2); bacteria--days 0, +6, RIL-2--days 0, +2, +4 (group 3). RIL-2 exerted no protective effect in group 1. However, in groups 2 and 3, where the control animals survival was, resp., 56% and 38%, the RIL-2 treatment increased survival up to, resp., 84% and 70%. Antibiotics given instead of RIL-2 in analogous regimen decreased the survival in group 3 to the level of 25%. Thus, RIL-2 proved to be a potent therapeutic agent in the 2nd of 3d studied models of S. aureus--induced peritonitis in mice. The perspectives of RIL-2 use in the treatment of bacterial peritonitis, including porous ones, and of the immunodepression--aggravated conditions are discussed.     

Protective effect of swerchirin on hematopoiesis in 60Co-irradiated mice.

The protective effect of swerchirin, a purified xanthone isolated from whole herb of Swertia calycina Franch. on hematopoiesis was investigated. A significant increase of colony formation in the spleen (colony forming unit in spleen = CFU-S) of mice irradiated with 550 rad 60Co gamma-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with swerchirin [10 mg/kg, 3 time/wk, i.p.] was observed. After introduction of swerchirin [10 mg/kg, i.p. once] a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor (CSF) were also confirmed. The types of CSF in serum were M-CSF and other hematopoietic growth factors, which were confirmed using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of swerchirin on hematopoiesis may be related to its activity inducing CSFs and other hematopoietic growth factors, and warrant further evaluation of its usefulness.     

The effect of hormones on experimental moniliasis in mice

Summary By inoculating testosterone or estradiol alone and in combination with cortisone and somatotrophic hormone into male and female mice infected with moniliasis, it was shown that these sex hormones play a major role in modifying the course of the infection in these animals. The use of testosterone indicated that it had a marked synergistic activity with cortisone in enhancing the severity of the infection for both sexes. In addition, a mixture of testosterone and cortisone inoculated into normal mice at dosage levels which displayed no toxic effect when either agent was used alone, displayed a marked toxicity for male animals.These data also support the contention that the sex of the animal plays a major role in governing the response of normal or infected animals treated with cortisone and/or somatotrophic hormones.The possible implication of these data clinically is discussed.This paper is part of a study supported by Contract No. NONR 717(00) between the Office of Naval Research, Department of the Navy, and the Creighton University.A preliminary report of this work has been presented (Scherr, 1954a).     

Inhibition of lymphoproliferative response and its restoration with a glucan immunomodulator in mice with experimental larval toxocarosis

A high infective dose ofToxocara canis eggs (2 500 eggs per mouse) induced a partial immunosuppression in mice, manifested by inhibition of the proliferative response of splenic T and B cells to polyclonal activators. A glucan immunomodulator given to infected animals at the beginning of the experiment showed a marked stimulative and restorative effect on the parasite-suppressed lymphoproliferative response. The ability ofT. canis to migrate in the host was reduced in glucan-treated animals by 27%.     

Liposomal muramyl dipeptide therapy of experimental M5076 liver metastases in mice

Summary The effectiveness ofN-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) or of liposomes containing a lipophilic MDP derivative, MDP-glyceroyldipalmitate MDP-GDP in inhibiting the growth of M5076 reticulum cell sarcoma liver metastases in C57BL/6 mice has been determined. MDP (100 µg) or liposomal MDP-GDP (2.5 µmol containing 1 µg) were equally effective in inhibiting liver metastatic growth when given as a single treatment 3 days before tumor cell injection. Therapeutic treatment, initiated 3 days after tumor cell injection and continued for a period of 2 weeks, failed to inhibit metastatic growth. Activation of thioglycollate-elicited peritoneal macrophages or Kupffer cells in vitro with MDP or liposomal MDP-GDP resulted in the expression of tumoricidal activity against M5076 tumor cells. Adoptive cellular therapy with four injections of 2 × 10⁶ macrophages was ineffective: activation of the macrophages with either MDP or liposomal MDP-GDP prior to injection was effective in inhibiting liver metastatic growth. Incorporation of the macrophage toxin dichlorodimethylene diphosphonate within liposomes containing MDP-GDP abolished the ability of such liposomes to induce macrophage or Kupffer cell tumoricidal activity in vitro as well as the antitumor activity when administered 3 days before tumor cell challenge.     

Modifying effect of water-soluble analogs of quinoid radiotoxins on hematopoiesis in gamma-irradiated mice

It was established that quinoid products of tyrosine oxidation, analogues of natural radiotoxins, when used in the studied doses decreased the radiosensitivity of spleen stem cells and enhanced the restoration of bone marrow cellularity of mice exposed to sublethal gamma-radiation doses.     

Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice

The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections.     

Effects of indomethacin on hematopoiesis in mice

The effect of indomethacin treatment on hematopoiesis in mice was examined. Twenty-four hours following the onset of treatment there was 3-fold increase in bone marrow non-specific esterase positive cells (NEPC) as compared to the initial level. Two days later a two-fold increase in spleen and peritoneal NEPC was observed.In all the organs examined, NEPC returned to its basal level after cessation of treatment. The increase in number of NEPC was accompanied by an elevation in CSF production. The effect of indomethacin on peripheral blood cells was also determined. A significant decrease in hematocrit level was found following the treatment. In addition, it was further found that following the drug treatment there was a significant reduction of erythrocyte number and hemoglobin levels     

The effect of fungizone on experimental adiaspiromycosis of laboratory mice

Summary In laboratory mice weighing about 25 g, with experimental infection of adiaspiromycosis, total inhibition of development of the parasitic phase of the agent of this mycosis is induced with Fungizone — Squibb in daily intraperitoneal administration of 0.03 mg (dissolved in 0.1 ml of isotonic saline). In autopsies carried out 10th, 20th and 30th day after an intraperitoneal inoculation of 1 ml suspension of the mycelial phase of two Czechoslovak isolates ofEmmonsia crescens Emmons &Jellison 1960, no elements of the parasitic phase — adiaspores were found in the organs of the treated mice. In control groups of the untreated mice, experimental infection developed which was demonstrated by macro- and microscopical controls of organs and by a successful recovery of the agent.     

The effect of pegylated antisense acetylcholinesterase on hematopoiesis

To determine whether the efficacy of entry and action of antisense oligonucleotides (AS-ODN) on hematopoietic stem cells in vitro could be improved by the addition of polyethylene glycol (PEG), a molecule of PEG was bound to AS- or sense-acetylcholinesterase (AS-ACHE or S-ACHE). The introduction of 0.1-0.5 microM PEG-AS-ACHE or 0.5 microM AS-ACHE into methylcellulose bone marrow (BM) cultures produced a doubling in number of colony-forming unit-granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM) and a 5-fold increase in cell number of the PEG-ODN. Further increase in concentration of the PEG-ODN reduced colony numbers. PEG-AS-ACHE induced higher colony numbers and greatly increased megakaryocyte (MK) formation when compared with PEG and AS-ACHE added separately to the culture. In addition, differentials of the CFU-GEMMs indicated there was a direct relationship between MK number and PEG-AS-ACHE concentration. Under these culture conditions, 5 microM PEG alone gave control values of CFU-GEMM. On addition of FITC-PEG-AS-ACHE to the cell cultures, using confocal microscopy, the nuclei of both early and mature MKs were labeled specifically, whereas all other cellular nuclei were negative to the stain. The use of PEG-AS-ODN, affording specific delivery of AS-ODN to target cells, increased cell proliferation, and enhanced ODN uptake, may be of potential importance in stem cell expansion for BM transplantation and gene therapy.     

The effect of erythrocyte polypeptides on the erythron system in experimental anemia]

The paper reports the action of the polypeptide preparation made of red cells on erythron system in rat toxic anemia. These polypeptides proved more effective as to erythropoiesis stimulation in phenylhydrasine anemia than vitamin B12 or lek. Red cell polypeptides are considered possible regulators of erythropoiesis.     

The effect of lysergic acid diethylamide on memory in mice]

In experiments on mice of the BALB/c strain a study was made of the influence of lysergic acid diethylamide (LSD) on the retention and reproduction of a conditioned passive avoidance reaction (CPAR). A 0.5-3.0 mg/kg of LSD Injected intraperitoneally 10 min. before the learning procedure, worsened the CPAR retention, while a 0.2 mg/kg of LSD Improved it. The drug (0.2 mg/kg) facilitated the retrieval of the reaction, which did not manifest itself in 24 and 48 hours after learning. This effect depended on the strength of the unconditioned stimulus presented during learning as well as on the time intervals between the moments of learning and testing. Facilitated CPAR retrieval was observed only during the action of the drug and disappeared in 24 hours after its administration. The possible physiological mechanisms of LSD influence on memory processes are discussed.     

The effect of interleukin-2 on experimental emotional hypertension]

The effect of human recombinant interleukin-2, one of the potent mediators of the immune system, on the course of emotional hypertension in non-linear white rats has been investigated. A significant and prolonged hypotensive action of a single injection of interleukin-2 in hypertensive rats has been revealed. The data obtained can be a new evidence of participation of immune system in the development of hypertension in experimental animals.