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Biomedical subjects

I Florentin

Publications and source records attributed to I Florentin.

At least 37 records · Page 2Linked to original sources
PubMed1986

Early changes in immune parameters induced by an acute nonantigenic inflammation in mouse: influence of imuthiol.

Calcium pyrophosphate (CaPP)-induced pleurisy, may represent one of the simplest expressions of inflammation in that the irritant is a non-diffusible, non-antigenic and non-pyrogenic agent. Spleen or lymph node T or B cell numbers and activities, as well as NK activity, were modified at distance by CaPP-pleurisy. An intense increase in blood polymorphonuclear cells was also triggered by the inflammatory process. Treatment with imuthiol (sodium diethyldithiocarbamate), an agent known to be active on the T-cell lineage, restored towards control values the inflammatory response and tended to normalize white blood cell percentages altered by the inflammatory process. The findings suggest imuthiol could be employed as a virtually nontoxic and non-steroidal anti-inflammatory agent.

Animals↗
PubMed1986

In vivo immunopharmacological properties of tuftsin (Thr-Lys-Pro-Arg) and some analogues.

Tuftsin (Thr-Lys-Pro-Arg) is part of the Fc fragment of a leukophilic IgG and is a stimulator of the phagocytic activity of macrophages and polymorphonuclear cells (PMN) when cleaved from its carrier molecule. Tuftsin was shown to stimulate in vitro all PMN and macrophage functions examined through binding to specific cell surface receptors. In the present work, we provide further evidence that synthetic tuftsin administered to mice may act as an immunomodulator and that its effects on immune functions may result from a primary action on macrophages. After i.v. injection at a dosage of 25 micrograms/mouse, tuftsin stimulated effector (phagocytosis) and regulatory (IL1 production) functions of macrophages and potentiated DTH reaction. Lymphocyte functions (proliferative response to mitogens, T cell-mediated cytotoxicity, IL2 and gamma IFN production) were depressed at times at which macrophage activities were maximally enhanced, suggesting that negative regulatory functions of these latter cells were also stimulated. Tuftsin analogues were synthetized representing substitution or derivatization of the threonyl residue. The relative potencies of these analogues in augmenting phagocytosis-induced chemiluminescence of macrophages were tuftsin greater than or equal to (Gly1)-tuftsin greater than for-tuftsin greater than (for-Met1)-tuftsin greater than (Met1)-tuftsin. Concerning potentiation of DTH reaction the order was (Gly1)-tuftsin greater than or equal to (for-Met1)tuftsin greater than tuftsin greater than (Met1)-tuftsin greater than for-tuftsin. In contrast to tuftsin, none of the analogues induced depression of spleen cell reactivity to mitogens. In addition, (for Met1)-tuftsin administration resulted in an increased production of IL2 and IFN by ConA-stimulated spleen cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1985

Modifications of host defence mechanisms by an acute non-immunological inflammatory reaction.

Mice developing an acute non-immunological inflammatory reaction were examined for modification of specific and non-specific defence mechanisms on the basis of previous observations that these animals displayed an increased resistance to bacterial and parasitic infections but an impaired resistance to neoplasia. Local acute inflammation was induced by injection into the pleural cavity of a non-antigenic, endotoxin-free irritant--calcium pyrophosphate microcrystals or low-molecular-weight dextran. Effector functions of macrophages at remote sites from the inflammatory focus were markedly stimulated. This was shown by: (a) an accelerated elimination of Listeria monocytogenes in the liver and spleen of mice with inflammation; (b) the acquisition of cytostatic activity for tumour cells by peritoneal macrophages; and (c) an enhancement of chemiluminescence emission and superoxide production in response to phagocytosis. Natural killer activity of spleen and peritoneal cells was stimulated in a biphasic manner. In contrast, cytolytic T cell differentiation upon in vitro immunization of spleen cells against allogeneic tumour cells was impaired. All these effects were observed very early (2 h) after the onset of inflammation and were still detectable at least 3 days after the inflammatory process had disappeared.

Animals↗
PubMed1985

Sodium diethyldithiocarbamate influences the early immunological changes evoked by an acute non-antigenic inflammation process.

Calcium pyrophosphate (CaPp) produces an acute local inflammatory process when administered intra-pleurally. It is the simplest model of an inflammation uncomplicated by pharmacological properties of the agent or the presence of an antigen. Spleen or lymph-node T- or B-cell numbers and activities, including NK activity, are modified within 2 h under these conditions. A treatment with sodium diethyldithiocarbamate (lmuthiol), already known as a T-cell augmenting agent, restores towards normal values both the inflammatory reaction and the modified immune parameters induced in mice by CaPp pleurisy. The use of lmuthiol as a non-toxic, non-steroidal antiinflammatory agent is therefore suggested.

Animals↗
PubMed1985

Release of interleukin I and low-molecular-weight lymphocyte-activating factors by rat peritoneal macrophages and its enhancement by acute non-specific inflammatory processes.

Peritoneal macrophages harvested from rats undergoing an acute non-specific inflammatory reaction induced by an injection of calcium pyrophosphate (CaPP) into the pleural cavity released increased amounts of interleukin I (IL-I)-like material. Lymphocyte-activating factors were also found in ultrafiltrates of the macrophage supernatants below 10 kd and 5 kd. A similar pattern of activity was observed when lysates of the macrophages were tested. In addition pre-exposure of normal peritoneal macrophages to an acute pleural inflammatory exudate before supernatant production enhanced the release of lymphocyte-activating factors found both in the unfractionated supernatant and a sub-5-kd ultrafiltrate. Thus these results demonstrate that an acute inflammatory reaction, initiated by a non-antigenic stimulus is able to stimulate macrophages remote from the inflammatory site to produce a factor which behaves like IL-I in a standard IL-I assay. The presence of low-molecular-weight factors (less than 5 kd) with similar activity may suggest that degradation of IL-I has taken place to yield active fragments. Acute inflammatory exudate also augments release of these factors which may be important in the pathogenesis of inflammation.

Animals↗
PubMed1984

Modification of the chemiluminescent response of rat thymocytes to concanavalin A by the acute non-specific inflammatory process.

Using the technique of concanavalin A-induced chemiluminescence (CL) as a measure of lymphocyte reactivity it has been demonstrated that the acute non-specific inflammatory process initiated by a non-diffusible, non-antigenic, endotoxin free irritant, was able to enhance the CL response of rat thymocytes. Maximum enhancement was observed 48 h after initiation of the inflammatory reaction. Serum derived from animals undergoing an acute inflammatory reaction as used above was fractionated using the technique of ultrafiltration to yield a fraction of molecular weight range 500-2000 daltons. When this fraction was cultured in vitro for 22 h with normal thymocytes, the CL response to concanavalin A was greatly enhanced when compared to thymocytes cultured in the presence of an equivalent fraction of normal serum. These findings demonstrate that during an acute non-immunological inflammatory reaction the function of the hosts thymocytes is enhanced. Furthermore, a low molecular weight factor (500-2000), with thymocyte stimulating activity, may be recovered from the serum of such animals very quickly (within 2 h) after initiation of the acute inflammation.

Animals↗
PubMed1984

An in vitro effect of an acute non-specific inflammatory serum on rat lymphocytes proliferative response to PHA.

This study has demonstrated that serum obtained from animals undergoing an acute inflammatory reaction induced by an intrapleural injection of dextran is able to modulate the proliferative response to PHA of lymph node and spleen cells in vitro. This response is dependent on the concentration of the inflammatory serum and on the time of collection of the serum during the acute inflammatory process. At low concentrations of serum (0.5%) stimulatory activity was observed at all time points. At higher concentrations (1%) inhibitory activity was present in 24 and 72 h sera. These results support the previous observation that the acute non-specific inflammatory reaction is able to modify the function of different cell types. It has been suggested that both stimulatory and inhibitory factors are present and the balance between these changes during the course of the inflammatory reaction.

Animals↗
PubMed1984

Modification of thymo-dependent and thymo-independent antibody responses during non-specific acute inflammation.

An acute non-immunological inflammatory reaction, induced in mice by injecting intrapleurally a non-bacterial, non-antigenic and endotoxin-free irritant (40,000 molecular weight dextran or monoclinic dihydrated calcium pyrophosphate microcrystals), provoked an increase of antibody responses to thymus-dependent SRBC or thymus-independent TNP-LPS or DNP-Ficoll when the phlogistic stimulus was applied before immunisation. The increase in the number of IgM plaque-forming cells per spleen was obtained for different time intervals between the induction of the inflammatory stimulus and the antigen administration according to the type of irritant and the antigen used. However, no stimulation could be observed when this time interval was greater than three days. No stimulation of the antibody response to SRBC was observed when the irritant was applied one to three days after the antigen. The (stimulatory) effect could not be entirely related to a polyclonal activation as an augmentation in the production of antibody against non-cross-reactive antigen could only be seen four days after the onset of the inflammatory process, when the specific antibody response was not maximal. These observations indicate that an acute non-immunological inflammatory reaction lasting for 48 h can affect the immune reactivity of the host, even after the inflammatory process has disappeared.

Acute Disease↗
PubMed1984

Direct and indirect in vivo stimulation of LAF-like production induced by acute nonspecific inflammatory processes.

Peritoneal macrophages harvested from animals undergoing an acute non-immunological inflammatory reaction induced by an injection of calcium pyrophosphate ( CaPP ) or dextran into the pleural cavity showed an enhanced level of production of a lymphocyte activating factor (LAF) like material. On the other hand, macrophages harvested from the site of inflammation did not show enhanced production of this activity when compared to macrophages derived from normal controls. This enhanced activity was observed for up to two/three days after initiation of the inflammatory reaction and was obtained in both the presence and absence of lipopolysaccharide (LPS) during in vitro cultivation. Thus these results demonstrate that the acute inflammatory reaction, initiated by a non-antigenic stimulus ( CaPP ), is able to stimulate macrophages remote from the inflammatory site to produce a factor which behaves like LAF in a standard LAF assay.

Animals↗
PubMed1984

In vivo effects of an acute nonimmunological inflammation in rats on the lymphoproliferative response to mitogens.

Lymphoid cells (spleen, lymph node and thymus) derived from rats after induction of an acute nonimmunological inflammatory reaction responded to various mitogens (Phytohemagglutinin, PHA; Concanavalin A, Con A; Lipopolysaccharide, LPS) with increased proliferation when compared with cells derived from normal animals. In the absence of mitogens, lymphoid cells from animals undergoing an acute nonimmunological inflammation demonstrated enhanced proliferation compared with cells from normal animals. These results clearly demonstrated that during acute nonimmunological inflammation the reactivity of lymphoid cells was increased.

Acute Disease↗
PubMed1984

Dichloromethylene diphosphonate (Cl2MDP) reduces natural killer (NK) cell activity in mice.

Daily administration of dichloromethylene diphosphonate (Cl2MDP) to (C57BL/6 X DBA/2) F1 hybrid mice, from two days of age (10 mg of P/kg body weight), resulted in a marked impairment of natural killer (NK) activity of spleen cells against YAC-1 lymphoma cells. The suppressive effect increased with the duration of the treatment. Cessation of the treatment led to a rapid recovery (in 2 weeks) of NK activity while the osteopetrotic bone lesions persisted. Thus, the loss of natural killing cannot be explained by the simple reduction of bone marrow volume secondary to Cl2MDP-induced osteopetrosis. However, as NK cells are considered to be dependent on the bone marrow because they cannot be sustained by extramedullary production, a direct effect of Cl2MDP on the generation of NK cell precursors by the bone marrow was not excluded. Cl2MDP was not directly toxic to the fully differentiated splenic NK cells, since the addition of Cl2MDP to the in vitro assay (10(-5)-10 micrograms/ml) did not reduce cytotoxicity. These studies suggest that impairment of NK activity during Cl2MDP treatment may have clinical toxicologic implications since NK cells have been suggested to play an important role in natural host defenses against infection and neoplasia.

Animals↗
PubMed1984

Rat and human polymorphonuclear leukocyte derived lymphocyte stimulatory factors.

The kinetic release of lymphocyte activating factors by inflammatory rat polymorphonuclear leukocytes (PMNs) into culture fluid was studied. PMNs, collected from the pleural cavity of rats 4 hours after injection of either calcium pyrophosphate (CaPP) or normal plasma, released into the supernatant culture fluid, factors which enhanced the phytohaemagglutinin-induced proliferative response of normal lymph node cells or thymocytes, the optimal culture time being 24 hours. A major portion of these lymphocyte activating factors was found in the ultrafiltrates (less than 10,000 daltons) of PMN supernatants. The activities in both unfractionated supernatant and the ultrafiltrate were significantly enhanced if PMNs were exposed to Concanavalin A (Con A) or inflammatory exudate prior to supernatant production. Also, these were not species specific as rat PMN supernatant can stimulate the phytohaemagglutinin-induced response of human lymphocytes and, conversely, human PMN factors can stimulate rat thymocytes.

Animals↗
PubMed1983

Antitumor activity of living or killed Brucella: modification of the non-specific cytotoxic effector cells.

At various times after injection of living or killed smooth (S) or rough (R) Brucella abortus mice received a graft of the semi-allogenic EL4 lymphoma and their survival was studied. In parallel, the NK activity of spleen and peritoneal cells, the level of serum interferon (IFN), and the cytotoxic activity of peritoneal macrophages were investigated. Protection against the lymphoma lasted longer after injection of R organisms than after S. The parallelism between the in vivo resistance to El4 lymphoma and the augmentation of NK and macrophage activity was satisfactory with R but not with S. IFN production did not seem to be correlated with R antitumor activity. The antitumor effect of Brucella cannot therefore be simply explained on the basis of modification of the non-specific cytotoxic effector mechanisms.

Animals↗
PubMed1983

Comparative analysis of the immunopharmacological properties of three new nitrosourea analogues: RPCNU, RFCNU and Chlorozotocin.

Three sugar derivatives of chloroethyl nitrosoureas: RPCNU, RFCNU and Chlorozotocin (CLZ) were examined for their effect on the immune system in mice when administered at the minimal antineoplastic therapeutic dose. When the drugs were administered 4 days prior to antigenic stimulation, a potentiation of DTH to oxazolone was observed whereas the antibody response to SRBC was markedly decreased. When injected 24 h after immunization, the nitrosourea analogues did not modify the intensity of DTH reaction and of allograft rejection and only RFCNU depressed the antibody response. The proliferative response of spleen cells to T or B cell mitogens was strongly depressed after in vivo treatment with either of the three analogues. Concomitantly, peritoneal macrophages became strongly cytostatic for tumor cells and also displayed an enhanced chemiluminescence upon phagocytosis. An augmentation of antibody-dependent cellular cytotoxicity of spleen cells was observed only after CLZ administration which also resulted in an increase of NK activity of peritoneal cells but in an inhibition of spleen cell cytotoxicity. This study demonstrates that the nitrosourea analogues act as immunomodulating agents and reinforces their interest as antineoplastic drugs since they can stimulate nonspecific effector mechanisms known to play a role in resistance against tumors.

Animals↗
PubMed1983

Acute non-specific inflammation and modification of macrophage and lymphocyte functions.

The acute inflammatory response is a common phenomenon experienced by the physician in a wide variety of clinical situations. One of the major problems facing the investigator in this field of research who wishes to look at the cellular and humoral responses involved, is that in most of the animal models previously used, the inflammatory reaction has been provoked in subcutaneous tissues. Thus, a quantitative assessment of leucocyte emigration and mediator production in the inflamed area is technically difficult without resorting to complicated and artificial methods. Inflammation provoked in the pleural cavity provides a useful tool in the study of these problems since the collection of cells and analysis of humoral factors in exudates is easily accomplished. Among the irritants that may be used, we focused our interest on calcium pyrophosphate (CaPP) crystals, a non-diffusible, non-antigenic and endotoxin-free irritant, because their deposition is implicated in pseudogout and chondrocalcinosis in man (MacCarty, 1973). Calcium pyrophosphate-induced pleurisy is typified by an acute reaction, dominated by polymorphonuclear leucocytes, reaching its maximal intensity at about 5 h and disappearing within 48 h (Willoughby et al., 1975). It was found to be independent of the complement system. Examination of the known mediators of inflammation revealed no significant participation of either histamine or 5-hydroxytryptamine. There was an early rise in PGE2 followed by a greater rise in PGF2 alpha as the reaction diminished (Capasso et al., 1975). More recently, we have demonstrated the presence of a small quantity of thromboxane and a large quantity of prostacyclin during the first 2 hours of this inflammatory process. It was also shown that this type of acute inflammation was accompanied by the very rapid liberation of acute phase proteins both locally, in the exudate, and systemically in the serum (Tissot et al., 1983). Some of these events were also examined during the pleural reaction to other types of irritants (Capasso et al., 1975) and gave similar results (Tissot et al., 1983).

Animals↗