Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

BACKGROUND/AIM: Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. METHODS: Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. RESULTS AND CONCLUSION: Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period.

Reduction of acute inflammation in rats by diazepam: role of peripheral benzodiazepine receptors and corticosterone.

Carrageenin causes a reproducible inflammatory reaction and remains the standard irritant for examining acute inflammation and anti-inflammatory drugs. High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin administration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosterone on the anti-inflammatory effects of diazepam. Five experiments were conducted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on carrageenin-induced paw edema (CIPE), pleurisy and increase in vascular permeability in rats. Results showed that: 1. diazepam or Ro5-4864 (a PBR agonist) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-benzodiazepine PBR antagonist) suppressed the effects of either diazepam or Ro5-4864 on CIPE; 3. diazepam reduced the volume of the pleural exudate in carrageenin-injected rats, as well as its leukocyte count; 4. diazepam treatment reduced the magnitude of the increase in vascular permeability caused by carrageenin; 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticosterone. These results suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.

Effects of social isolation on ehrlich tumor growth and tumor leukocyte infiltration in mice: evidence of participation of the submaxillary salivary gland.

OBJECTIVE: Considering previous studies on stress and Ehrlich tumor growth from our laboratory and also known cell growth and behavior-related properties of submaxillary salivary gland products, we studied the effects of stress by social isolation, in combination or not with sialectomy (submaxillary gland ablation), on growth and leukocyte infiltration into Ehrlich adenocarcinomas. METHODS: 5 x 10(7) tumor cells/ml were inoculated into the footpads of mice and tumor growth was evaluated by measuring paw thickness on alternate days. Ten days after inoculation, tumors were harvested and processed for immunocytochemical analysis of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK cell and macrophage percentages were calculated. RESULTS: Sialectomy slightly reduced tumor growth and caused a significant increase in NK cell infiltration of tumors (p < 0.05). Social isolation caused a highly significant enhancement of both tumor growth (p < or = 0.05) and percentage of macrophages infiltrating tumors (p < 0.05). Sialectomized isolated animals showed few significant changes in tumor growth rate (p < or = 0.05), but presented increased percentages of NK cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen only in 8-month-old mice, but not in younger animals. CONCLUSION: A possible link between salivary gland factors, tumor growth and TIL patterns was considered, suggesting that growth factors may modulate tumor leukocyte infiltration as well as tumor growth rate.

Effects of high doses of diazepam on carrageenin-induced paw edema in rats.

Benzodiazepine (BDZ) receptor sites play a relevant role in immune/inflammatory reactions. Acute BDZ treatments were shown not only to suppress cell proliferation in rat thymus but also to decrease TNF-alpha, IL-1 and IL-6 release from adult mouse macrophages. In the present investigation the effects of acute (10.0 and 20.0 mg/kg) and long-term (10.0 mg kg-1 day-1, for 21 days) diazepam treatment on carrageenin-induced paw edema were studied in rats. The results showed that acute treatment with high doses of diazepam decreased paw edema volume in a dose-dependent manner, and this effect was observed as early as 1 h after the administration of the 20.0 mg/kg dose and continued until the last measurement was performed (8 h). In contrast, long-term diazepam administration did not modify the phlogistic-induced edema. Taken together, these data show that 1) acute diazepam treatment with high doses decreases the volume of the acute inflammatory paw edema developed by the organism as a response to carrageenin-induced injury, and 2) long-term diazepam treatment induces tolerance to this effect. These results are discussed in the light of a possible effect of diazepam on the components of the rat cellular and humoral immune/inflammatory reaction such as T lymphocytes and/or interleukins.

Effects of high doses of diazepam on carrageenin-induced paw edema in rats

Benzodiazepine (BDZ) receptor sites play a relevant role in immune/ inflammatory reactions. Acute BDZ treatments were shown not only to suppress cell proliferation in rat thymus but also to decrease TNF-alpha, IL-1 and IL-6 release from adult mouse macrophages. In the present investigation the effects of acute (l0.0 and 20.0 mg/kg) and long-term (10.0 mg kg(-1) day(-l), for 21 days) diazepam treatment on carrageenin-induced paw edema were studied in rats. The results showed that acute treatment with high doses of diazepam decreased paw edema volume in a dose-dependent manner, and this effect was observed as early as 1 h after the administration of the 20.0 mg/kg dose and continued until the last measurement was performed (8 h). In contrast, long-term diazepam administration did not modify the phlogistic-induced edema. Taken together, these data show that 1) acute diazepam treatment with high doses decreases the volume of the acute inflammatory paw edema developed by the organism as a response to carrageenininduced injury, and 2) long-term diazepam treatment induces tolerance to this effect. These results are discussed in the light of a possible effect of diazepam on the components of the rat cellular and humoral immune/inflammatory reaction such as T lymphocytes and/or interleukins.

Substance P does not modify mononuclear cell migration into Ehrlich tumor mass.

In the present study, seven adult male mice were inoculated with Ehrlich tumor into the footpad after local substance P release was blocked by neurectomy of the sciatic and saphenous nerves. The contralateral footpad was also inoculated but sham-operated, and used as control. This procedure did not modify the percent of CD4+ (about 1-2%), CD8+ (about 1-3%), macrophages (about 21-22%), lymphocyte B (about 0-1%) and NK (about 1-2%) mononuclear cells present among tumor cells. These data suggest that chemotactic activity of substance P may not be relevant in this situation because the lack of this neurotransmitter (checked by immunohistochemistry) secondary to neurectomy did not change the cell migration profile into tumor mass.

Substance P does not modify mononuclear cell migration into Ehrlich tumor mass

In the present study, seven adult male mice were inoculated with Ehrlich tumor into the footpad after local substance P release was blocked by neurectomy of the sciatic and saphenous nerves. The contralateral footpad was also inoculated but sham-operated, and used as control. This procedure did not modify the percent of CD4+ (about 1-2 per cent), CD8+ (about 1-3 per cent), macrophages (about 21-22 per cent), lymphocyte B (about 0-1 per cent) and NK (about 1-2 per cent) mononuclear cells present among tumor cells. These data suggest that chemotactic activity of substance P may not be relevant in this situation because the lack of this neurotransmitter (checked by immunohistochemistry) secondary to neurectomy did not change the cell migration profile into tumor mass.

Influência da baixa temperatura ambiental sobre a atividade fagocítica de trombócitos de rä touro gigante (Rana catesbeiana) / Influence of low environmental temperature on the phagocytic activity of bullfrog (Rana catesbeiana) thrombocytes

O objetivo do presente trabalho foi o de investigar a influência da baixa temperatura ambiental sobre a atividade fagocitária de trombócitos de rä touro gigante (Rana catesbeiana). O modelo indutor de fagocitose utilizado foi a injeçäo de carväo coloidal no saco linfático dorsal. Os resultados alcançados mostraram que o frio foi capaz de modular significativamente a capacidade fagocítica dos trombócitos. Animais tratados e mantidos a 6§C exibiram uma lenta atividade inicial à 1h (16,3 mais ou menos 4,3; resultados expressos com média desvio padräo de trombócitos positivos em 400 células analisadas/animal; n=6), que aumentou discretamente às 6h e 12h (45,8 mais ou menos 12,2; 55,5 mais ou menos 9,6), alcançando o máximo de reaçäo aos 3d e 7d (80,3 mais ou menos 27,5; 78,3 mais ou menos 29,5). Por outro lado, räs mantidas a 24§C apresentaram uma forte resposta inicial à 1h (90,0 mais ou menos 16,7), aumentando marcadamente até 1d (196,0 mais ou menos 49,8), e entäo diminuindo até 7d (56,0 mais ou menos 10,6). Os resultados obtidos suportam estudos prévios que demonstram a importância da temperatura ambiental sobre múltiplos processos relativos aos mecanismos de defesa desses animais

The influence of social isolation and peripheral innervation on Ehrlich tumor growth in mice.

The relationship between social isolation and Ehrlich tumor growth was investigated in seven male NIH mice about 2 months old living separately in small cages for 28 days. Fifteen control animals were kept grouped in conventional cages (10 animals in one and 5 in another) for the same period. After this period, 40 to 50 microliters of a cell tumor suspension at a concentration of 1 to 5 x 10(7) tumor cells/ml was inoculated into the footpad and footpad size was measured for 10 days. Isolated mice presented a 30% reduction in tumor growth. Sciatic and saphenous neurectomy in one leg of 5 isolated mice (experimental) and 5 grouped mice (control) performed 7 days before tumor inoculation abolished this difference, and more tumor growth was observed in the neurectomized paw compared to the non-neurectomized paw. The subordinate x dominant social relationship established between mice living in groups of two per cage (seven cages) did not modify the growth of tumor inoculated under the same conditions compared to the first experiment. We conclude that social isolation and an intact peripheral innervation are associated with reduced tumor growth, but dominance behavior has no effect.

The influence of social isolation and peripheral innervation on Ehrlich tumor growth in mice

The relationship between social isolation and Ehrlicha tumor growth was investigated in seven male NIH mice about 2 months old living separately in small cages for 28 days. fifteen control animals were kept grouped in conventional cages (10 animals in one and 5 in another) for the same period. After this period, 40 to 50 µl of a cell tumor suspension at a concentration of 1 to 5 x 10**7 tumor cells/ml was incolulated into the footpad and footpad size was measured for 10 days. Isolated mice presented a 30 percent reduction in tumor growth. Sciatic and saphenous neurectomy in one leg of 5 isolated mic (experimental) and 5 grouped mice (control) performed 7 days before tumor inoculation abolished this difference, and more tumor growth was observed in the neurectomized paw compared to the non-neurectomized apw. The subordinate x dominant social relationship established between mice living in groups of two per cage (seven cages) did not modify the growth of tumor inoculated under the same conditions comapared to the first experiment. We conclude that social isolation and an intact peripheral innervation are associated with reduced tumor growth, but dominance behavior has no effect

Chronically inflamed tissue activates plasma mediators of vascular permeability.

1. After inflammation was induced in the foot-pad of rats with nistatin or BCG, injection of "non-activated" homologous plasma at the inflamed site caused a significant increase in the vascular permeability of the lesions (Evans blue test), which was more intense in older lesions, increasing from 7.83 +/- 1.11 to 8.70 +/- 1.18 (nistatin, 4 and 21 days) and 7.30 +/- 0.66 to 7.54 +/- 0.80 (BCG, 4 and 21 days). 2. Steroidal (acetyltriamcinolone, 2 mg/kg) and non-steroidal (indomethacin, 25 mg/kg) [corrected] anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 +/- 0.10 for acetyltriamcinolone treatment vs 8.15 +/- 1.22 for untreated animals; 3.34 +/- 0.41 for indomethacin treatment vs 8.15 +/- 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 +/- 0.11 for acetyltriamcinolone treatment vs 10.27 +/- 0.52 for untreated animals; 5.87 +/- 0.35 for indomethacin treatment vs 9.14 +/- 0.23 for untreated animals). 3. These data suggest that an increase in exudation in chronic lesions might result in "reactivation" of the process as observed clinically, for example, in rheumatoid arthritis in man.

Hyperosmotic sodium chloride partially blocks the effects induced by Bothrops jararaca venom on vascular permeability and hemorrhage in the rat.

The effect of the administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on hemorrhage and vascular permeability changes induced by Bothrops jararaca venom in rats was determined 30 min after venom injection. This treatment given immediately after subcutaneous venom injection significantly reduced the hemorrhagic manifestations by 33%. The increase in vascular permeability was significantly reduced when the animals were pretreated with hyperosmotic saline or mannitol 15 min before receiving the venom (26% and 20%, respectively). However, when animals were treated immediately after venom injection, only the hyperosmotic NaCl solution significantly reduced vascular permeability (32%). Isotonic NaCl treatment had no effect on hemorrhagic lesions or vascular permeability.

Chronically inflamed tissue activates plasma mediators of vascular permeability

After inflammation was induced in the foot-pad of rats with nistatin or BCG, injection of "non-activated" homologous plasma at the inflamed site caused a significant increase in the vascular permeability of the lesions (Evans blue test), which was more intense in older lesions, increasing from 7.83 + or - 1.11 to 8.70 + or - 1.18 (nistatin, 4 and 21 days) and 7.30 + or - 0.66 to 7.54 + or - 0.80 (BCG, 4 and 21 days). Steroidal (acetyltriamcinolone, 25 mg/kg) and non-steroidal (indomethacin, 2 mg/kg) anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 + or - 0.10 for acetyltriamcinolone treatment vs 8.15 + or - 1.22 for untreated animals; 3.34 + or - 0.41 for indomethacin treatment vs 8.15 + or - 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 + or - 0.11 for acetyltriamcinolne treatment vs 10.27 + or - 0.52 for untreated animals; 5.87 + or - 0.35 for indomethacin treatment vs 9.14 + or - 0.23 for untreated animals). These data suggest that an increase in exudation in chronic lesions might result in "reactivation" of the process as observed clinically, for example, in rheumatoid arthritis in man

Hyperosmotic sodium chloride partially blocks the effects induced by Bothrops jararaca venom on vascular permeability and hemorrhage in the rat

The effect of the administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on hemorrhage and vascular permeability changes induced by Bothrops jararaca venom in rats was determined 30 min after venom injection. This treatment given immediately after subcutaneous venom injection significantly reduced the hemorrhagic manifestations by 33%. The increase in vascular permeability was significantly reduced when the animals were pretreated with hyperosmotic saline or mannitol 15 min before receiving the venom (26% and 20%, respectively). However, when animals were treated immediately after venom injection, only the hyperosmotic NaCl solution significantly reduced vascular permeability (32%). Isotonic NaCl treatment had no effect on hemorrhagic lesions or vascular permeability

Do connective tissue components induce plasma activation in vivo?

1. This paper describes the effect of homologous plasma in contact with connective tissue on vascular permeability, edema and cell migration. 2. The contact of "non-activated" plasma with connective tissue structures does not result in generation of mediators responsible for increase in vascular permeability or in edema. 3. "Activated" plasma is able to induce vascular permeability and edema when in contact with connective tissue components. 4. Injection of "non-activated" or "activated" plasma induced a mild inflammatory cell migration.

Effect of i.v. administered hyperosmotic sodium chloride on carrageenan-induced pleurisy in adrenalectomized and intact rats.

The effect of administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on carrageenan-induced pleurisy was determined in adrenalectomized and intact rats. The volume of the pleural exudate was significantly reduced 4 h after induction by treatment with hyperosmotic NaCl for both adrenalectomized (0.08 +/- 0.16 ml) and intact (0.03 +/- 0.08 ml) animals compared to their untreated controls (0.56 +/- 0.44 ml and 0.26 +/- 0.15 ml, respectively). Similarly, hyperosmotic NaCl treatment significantly reduced the total number of inflammatory cells in the pleural cavity: 29.60 x 10(6) +/- 7.80 x 10(6) cells for adrenalectomized animals and 28.90 x 10(6) +/- 11.43 x 10(6) cells for intact animals compared to 63.67 x 10(6) +/- 19.92 x 10(6) and 45.26 x 10(6) +/- 12.71 x 10(6) cells for their untreated controls. Treatment with isotonic saline did not affect carrageenan-induced pleurisy. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.

Do connective tissue components induce plasma activation in vivo?

1. this oaoer describes the effect if homologous plasma in contact with connective tissue on vascular perveability, edema and cell migration. 2. The contact of "non-activated"plasma with connective tissue structures does not tesults in generation of mediators responsible for increase in vascular premeability or in edema. 3. "Activated" plasma is able to induce vascular permeability and edema when in contact with connective tissue components. 4. Injection of "non-activated" or "activated" plasma induced a mild inflammatory cell migration

Effect of iv administered hyperosmotic sodium chloride on carrageenan-induced pleurisy in adrenalectomized and intact rats

The effect of administration of hyperosmotic NaCl (2ml, 7.8% NaCl, iv) on carregeenan induced pleurism was determined in adrenalectomized and intact rats. tThe volume of the pleural exudate was significantly reduced 4 h after induction by treatment with hyperosmotic NaCl for both adrenalectomized (0.08 - 0.16 ml) and intact (0.03 - 0.08 ml) animals compared to their untreated controls (0.56 - 0.44 ml and 0.26 - 0.15 ml, respectively). Similarly, hyperosmotic NaCl treatment significantly reduced the total number of inflammatory cells in the pleural cavity: 29.60 x 10**6 cells for adrenalectomized animlas and 28.90 x 10**6 ñ 11.43 x 10**6 cells for intact animals compared to 63.67 x 10**6 cells for their untreated controls. Tretament with isotonic saline did not affect carrageenan-induced pleurisy. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response

Effect of hyperosmotic sodium chloride solution on vascular permeability and inflammatory edema in rats.

This study analyzes the effects of treatment with a hyperosmotic NaCl solution on carrageenan-induced inflammatory edema and vascular permeability in rats. Given 15 min before carrageenan, this treatment reduced paw edema measured for up to 6 h by 27 to 44%. Similarly, when the rats were treated 30 min after injection of the irritant, paw volume was significantly reduced (35 to 53%) between 1 and 6 h when compared to that of untreated animals. Increases in vascular permeability were significantly reduced at 30 min (73%) and 1 h (54%) in rats treated 15 min before, and at 1 h (49%) in animals treated 30 min after carrageenan. Treatment with hyperosmotic mannitol or isotonic NaCl solutions did not show any changes in inflammatory response to carrageenan. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.