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Biomedical subjects

R Neta

Publications and source records attributed to R Neta.

At least 73 records · Page 4Linked to original sources
PubMed1987

Enhanced hematopoietic recovery in irradiated mice pretreated with interleukin-1 (IL-1).

Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57Bl/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and day 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice. However, as determined by sensitivity to hydroxyurea, rIL-1 injection stimulated GM-CFC into cell cycle. These results demonstrate that rIL-1 injection increases the number of CFC that survive in irradiated mice and may be a consequence of the stimulation of CFC into cell cycle prior to irradiation.

Animals↗
PubMed1987

Tumor necrosis factor/cachectin is a less potent inducer of serum amyloid A synthesis than interleukin 1.

Serum amyloid A (SAA) gene expression is known to be induced by interleukin (IL-1). The time course of in vivo induction of SAA synthesis by IL-1 was found to vary according to dose, in that SAA concentration was maximal at 6 hours following lower doses of IL-1, but greater at 20 hours when higher (greater than 500 ng) doses were administered. Because of recent reports that recombinant human tumor necrosis factor/cachectin (TNF) is a pyrogen similar to IL-1, its efficacy as an inducer of SAA synthesis was analyzed. TNF was found to be at least 100 fold less potent that IL-1 on a weight basis in both C3H/HeJ and C57BL/6 mice. However, C3H/HeJ mice were found to be more sensitive than C57BL/6 mice to both IL-1 and TNF stimulated SAA production. The magnitude of the acute phase SAA response was therefore found to be a function of the type of inflammatory mediator and genetic factors in the host.

Animals↗
PubMed1986

Interleukin 1 is a radioprotector.

Pretreatment with recombinant interleukin 1 (IL 1) protects mice in a dose-dependent manner from lethal effects of ionizing radiation. Two thousand units of IL 1, given i.p. 20 hr before irradiation, protect 88% of C57B1/6 mice from an LD100/17 radiation dose (dose of radiation that kills 100% mice in 17 days), and 1000 U of IL 1 protect 100% of DBA/1 mice from an LD50/30 dose. This finding provides the first evidence that a cytokine, IL 1, which acts as a differentiation- and maturation-inducing agent for a variety of cells, also can serve as a signal that initiates radioprotective events in vivo. Because many of the exogenous immunomodulators that have been shown to be radioprotective also induce endogenous IL 1 production, our observation suggests that IL 1 may mediate their radioprotective effects.

Adjuvants, Immunologic↗
PubMed1986

Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma.

Immunomodulatory agents are radioprotective when administered to animals prior to irradiation. The mechanisms for this radioprotection have as yet not been determined, but may involve endogenously released cytokines. We have recently demonstrated that murine IL-1 is radioprotective in mice (Neta et al. J. Immunol., 136, 2483, 1986). In this study we have further explored this effect and investigated whether the radioprotective effect of IL-1 is mediated by other cytokines. Optimal radioprotection with IL-1 was obtained with administration 20 hr prior to irradiation and was greatly reduced with administration 45 or 4 hr before or 1 hr after irradiation with 950 cGy, an LD100/30 dose. The dose reduction factor (DRF) measured by LD50/30 was 1.25 for C57B1/6 mice. The presence of a lag period in IL-1 induced radioprotection suggests that the effect of IL-1 may be indirect. The hypothesis that IL-1 may act by inducing the release of other cytokines was tested in part by two approaches: Assays for circulating IFN and CSF. High titers of CSF were present at 3 and 6 hrs and declined at 24 hrs after administration of 0.1 microgram of IL-1, a dose radioprotective in mice. Assays for IFN in the same sera were negative. Direct administration of recombinant IFN-gamma, GM-CSF, or IL-2 prior to LD100/30 irradiation. Using a wide range of doses of these cytokines delivered 20 or 3 hr prior to irradiation, no significant radioprotective effect was observed.

Animals↗
PubMed1985

Thymic hormones in radiation-induced immunodeficiency. I. Induction of mature interleukin 1 responsive cell in the thymus by thymosin fraction 5.

The restorative effect of thymosin fraction 5 (TF5) on the thymus of gamma-irradiated mice was examined. Four different mouse strains were used in this study since earlier work determined that the degree of response to TF5 is strain dependent. The responsiveness to comitogenic effect of interleukin 1 (IL-1) was used to measure the rate of recovery of immunocompetent cells in the thymus, since only more mature PNA-, Lyt-1+-2- medullary cells respond to this monokine. Contrary to several earlier reports that radioresistant cells repopulating the thymus within the first 10 days after irradiation are mature, corticosteroid resistant, immunocompetent cells, the thymic cells from irradiated mice in all strains used had greatly reduced responses to IL-1. Daily intraperitoneal injections of TF5 increased significantly the responses of thymic cells to IL-1 in 10- to 13-weeks-old C57Bl/KsJ, C57Bl/6, C3H/HeJ, and DBA/1 mice. Older mice, 5 months or more in age, of DBA/1 strain did not respond to treatment with TF5. However, C3H/HeJ mice of the same age were highly responsive. In conclusion, (1) cells repopulating the thymus within 12 days after irradiation contain lower than normal fraction of mature IL-1 responsive cells, (2) thymic hormones increase the rate of recovery of immunocompetent cells in the thymus, and (3) the effect of thymic hormones is strain and age dependent.

Animals↗
PubMed1983

Resistance and susceptibility to infection in inbred murine strains. I. Variations in the response to thymic hormones in mice infected with Candida albicans.

Nine inbred murine strains were either highly resistant or highly susceptible to intravenous challenge with 4 X 10(4) to 1 X 10(5) cells of Candida albicans. The resistant strains had the capacity to develop delayed footpad reactions on appropriate sensitization and challenge; the susceptible strains did not have this innate capacity. Administration of thymosin fraction 5 beginning on the day of infection greatly increased the resistance of the susceptible strains to infection, but decreased the resistance of the resistant strains. In contrast, thymosin fraction 5 enhanced the delayed footpad responses of resistant-sensitized mice to specific antigen, but did not have a detectable effect on the delayed footpad reactions of the susceptible strains. Reinfection of the two types of strains had different effects, in that, depending on the strain, resistance could be increased, decreased, or not influenced at all.

Animals↗
PubMed1983

Resistance and susceptibility to infection in inbred murine strains. II. Variations in the effect of treatment with thymosin fraction 5 on the release of lymphokines in vivo.

Of nine inbred murine strains sensitized intravenously with killed lyophilized Candida albicans and challenged 3 weeks later with a C. albicans filtrate, four strains were low responders and five were high responders in the in vivo release of migration inhibitory factor (MIF) and gamma interferon (IFN-gamma). An identical distribution of high- and low-responder strains occurred in response to sensitization with Mycobacterium bovis BCG and subsequent challenge with old tuberculin. Treatment of the murine strains with thymosin fraction 5 prior to sensitization and challenge had different effects: (a) the high-responder strains had a decrease in their release in vivo of the two lymphokines; (b) three of five of the low-responder strains had a striking increase in the in vivo release of MIF and IFN-gamma; and (c) one low-responder strain did not have its response altered. A parallelism existed between the capacity of a murine strain to release the two lymphokines in vivo on stimulation with C. albicans antigens and the capacity of that strain to resist intravenous infection with living C. albicans.

Animals↗
PubMed1981

Mechanisms in in vivo release of lymphokines. III. Separation of gamma-interferon (IFN gamma) from cytotoxicity in inbred strains of mice.

Inbred strains of mice sensitized with BCG and challenged with old tuberculin (OT) vary in their capacity to release IFN gamma and MIF into circulation. Experiments were performed to correlate the presence of IFN gamma with that of the cytotoxic effect in an attempt to learn whether these two activities in the sera may be separated. Sera from eight inbred strains were obtained at times after challenge and assayed for IFN and for cytotoxic activity. A correlation did not exist between the titers of IFN gamma and the levels of cytotoxicity, i.e. sera from RF/J mice without detectable titers of IFN gamma had cytotoxic activity, while sera from C57BL/KsJ mice that had titers of IFN gamma were not cytotoxic. Regulation of IFN gamma titers could be achieved by administration of complete Freund's adjuvant to BCG sensitized mice. However, similar differences were not detected in cytotoxic activity. Therefore, IFN gamma may be released, or the activity of IFN gamma may be expressed in the circulation, in the absence of cytotoxicity.

Adjuvants, Immunologic↗
PubMed1981

Mechanisms in the in vivo release of lymphokines: relationship of high and low responsiveness to other parameters of the immune response.

Variations exist between different strains of inbred mice in the release of lymphokines into the circulation. A number of manifestations of cell-mediated immunity in mice sensitized intravenously with Mycobacterium bovis BCG were analyzed to determine their association with the in vivo release of gamma interferon (IFN-gamma) and migration inhibitory factor. Differences occurred among the strains in the proliferative responses of splenic cells to specific antigen and in the release of IFN after the challenge of BCG-sensitized mice with lipopolysaccharide. However, the capacity of an individual strain to release migration inhibitory factor and IFN-gamma into the circulation did not parallel the extent either of the proliferative responses or of the release of IFN induced by lipopolysaccharide. Not all of the strains developed marked delayed footpad reactions to challenge with PPD regardless of the extent of their responses by other parameters. Delayed footpad reactions did develop in mice sensitized via the subcutaneous route, although this sensitization did not result in the capacity to release migration inhibitory factor and IFN-gamma into the circulation of individual inbred strains.

Animals↗
PubMed1979

Adjuvants in the induction of suppressor cells.

The effect of different mycobacterial adjuvants on the parameters of delayed hypersensitivity was investigated in strain 13 guinea pigs. The composition of the tubercle bacilli and the type of vehicle in which the antigen was presented determined the presence and extent of suppressor cell activity. When antigen was introduced in complete Freund adjuvant, both adherent and nonadherent cells had suppressive properties, with the suppressive effect demonstrable in vitro from 1 to 5 weeks after sensitization. Suppressor activity was indicated in vivo by a reduction of delayed footpad hypersensitivity in animals presensitized with complete Freund adjuvant.

Adjuvants, Immunologic↗
PubMed1976

T and B lymphocytes in the regulation of delayed hypersensitivity.

A correlation was demonstrated between the transient nature of a) delayed intradermal responses of guinea pigs sensitized to hen egg albumin in incomplete Freund's adjuvant and b) the proliferative response of sensitized lymphocytes to the specific antigen. Spleen cells from sensitized animals suppressed the proliferative response of lymph node cells to specific antigen. This suppression was dependent on the dose of spleen cells and the time of their removal after sensitization. Thymus cells were suppressive to a lesser extent, and their activity was not correlated with the time of removal after sensitization. Separation of spleen and thymus cells into T and B populations indicated that the B cell was the major suppressor cell in the spleen, while the T cell in the thymus had a similar but less pronounced action.

Animals↗