- Email: [email protected]
A-adrenoreception in experimental meningococcal intoxication
P o s t e r A b s t r a c t s / J o u r n a l o f N e u r o i m m u n o l o g y 9 0 (1998) 1 3 - 1 0 5
41
215 A-Adrenoreception in Experimental Meningoeoccal Intoxication
218 Antidepressants as Neuroimmunomodulators at Postreceptor Level
,I, Karpov, W. Sbeiti, A. Sampson, MinskMedicalInstitution,Belarus,A. Milutin,
H. Kovaru. Charles University,CzechRep., A. Fiserova, AcademyofScience, Czech Rep., A. Spnaova, Masaryk University,CzechRep., V. Lisa, Academyof Science, Czech Rep., Z. Fisar, CharlesUniversity,CzechRep, J. Velek, Academyof Science, CzechRep.
Minskgcological College,Belarus
Mcllingococcul lneningitls is often accompanied by tneningococeentia ;-lud infectious toxic shock. In correct trealmen! of such patients physician unlsl take illtU aco0unt IIw, stage i1[ adrenoreccption, which Call canse severe hypotonia "file expcritnc1|lzl Ineltingncoccu] intoxicatiun was t.odcll~:d wilh inlravenous injection of meningoc0ecal LPS to 12 rabbits 1400-16tl0g weight nndcr thc lighl ba~t~iraratic narcosis. The quantity of ~-adrtmorecepfurs in lencocylic mcuthranes was teste.d us'ing radioligalld mclhod. Tlle low tltt;,mlilynf tx-adrenore,ceptur$ was detected during file inloxicatiun. The lowest rate was in te,rlnlinal singes of itttnaicatlon 78,4 ./.15,6 fl,ol\mg (ccnlllul 3(14,5+_54,4 fmolhalg). "llles, the decrease of adrenoreception K~;one of the intporlaltt Inechanisms in contp]icaled menmgococeal infectinn and it should be taken into aecoonl dining early intensive care.
216 I-Iistiostrueture of the MRL-1 Miees Thymus, Spleen and Nonapcptidergie Centres of the Hypothalamus During Correction of Autoimmune Pathology A.A. Stadnikov, L.N. Shishkanova, ~ S.O. Mitryakov, A.M. Mikhailov, V.A. Valeev, L.A. Lepatinskaya, StateMedicaIAcademy,Russia
Were used 43 MBL-I mice, a~ed 3-5 monthes, with ~enetically determined autoimmune pathology. They were separated for ~roups de~endinff from the treatment. It included: dic~ofenac-natrium, interrupted adaptation for h y p o b a r i c hypoxia condition, and both of these methods. Material were studied by light-optical, electron microscopy and morphometry. Our investi[ation revealed some disordes of neurosecretory process at the nonapeptiderffic centres and obstruction of neuropeptides excretion to the blood. No one correction method have not significantly normalized cytophysiolo[ical processes in investi~ated orffans. More positive dynamic were noted in male mice, then female, especially usin~ both of diclofenac and baroadaptation.
Antidepressants can evoke alterations in cell signalling including hetcrotrimeric GTP-binding (G) proteins. We used rat C6 glioma cell Imc. C6 cells transfected (t) with pig thymus lymphocyte markers (MHC 11, CDd, pan T, etc)(1) and natural killer (NK) lymphocy'tes. We analyzed postreceptor effects ofsertraline. SEIL (Pfizer) flnoxeline, FLU, and mnclobemide, MOC. (Roche). We studied changes of Go. subumts (Gq/l 1, Gs, Gil.2) using ELISA and Western immunoblotting (2.3). MOC effects are linked to changes in Gots/Gcxil,2 as supported by our in vivo studies. We demonstrated FLU effects on decreased level ofC,mt q/l I in both C6- and human NK cells, in contrast t o (t)C6 cells regulated by Gas and G~ (i 1,2). We observed FLU induced Cax q/l I down regulation accompanied with lower IP3 level (PLC effector). SER effects were linked to adenylyl cyclase via Gets and purinoceptor (adenosine receptor) coupled G protein effects were not accompanied by, apoptosis, whereas FLU affected this pathway with subsequent apoptic evems. Ref.: l.Kovgff=et al. (this congress). 2. Kovm~t'tet aL Proe Royal MicnSoc., 1997.Pt2 : 123. 3.Kovfifflet al. Acta Vet.Brno. 1998.67 (accepted). Supportedby grants ofGA (~R 309/95/1121. GAUl( 143/97 and partially by Pf~er and R~x:heCo.
219 T h e Suppressive Effect of A n t i d e p r e s s a n t D r u g s on the I m m u n i t y of Stressed A n i m a l s M. Kubera, InstituteofPharmacologyPAS,Poland, V. Holan, Institute ofMolecular Genetics, CzechRep., A. Basta-Kaim, J. Borycz, A. Rum an, E. Nowak, Institute of
PharmacologyPAS,Poland
The study was aimed at examining the influence of single and repeated administration of antidepressant drags (amitriptyline, desipramine, fluoxetine and citalopram) in a dose of 10 mg/kg i.p. on the immunity of animals subjected respectively to a single swimming stress, or to a chronic action of mild stressor stimuli (an aminal model of depression). The immunity was assessed, among others, by the ability of splenocytes to proliferate and synthesize cytokines (ILq. II.,.-2, 11,-4, IL-6, IL-I0 and IFN--I). It was found that both single and chronic administration of the above-mentioned drugs to stressed animals induced a decrease in majority of parameters studied, whereas those drugs per se produced an opposite effect. The stress itself did not affect most of the paramours tested; however, in part of the chronically stressed animals a significant increase in IL-I synthesis was observed.
217
220
Neuroendocrine M e d i a t o r s U p r e g u l a t e o~l-Adrenergie Receptors
N e u r o - l m m u n e R e l a t i o n s h i p s Studied with P E T M. Lekander. KarolinskaHospital, Sweden, M. Fredrikson, UppsalaUniversity,
on Monocytes A. Kavelaars. C. Rouppe vd Voort, M. van de Pol, C.J. Heynen, UniversityChildren
Sweden,O. wik, Martin-Luther Universitaet,Germany
Hospital Utrecht,Netherlands
Children with Juvenile Chronic Arthritis have an aberrant response of the immune system to catecholamines. Peripheral blood mononuclear cells (PBMC) of these patients respond to at-adrenergic activation with an increased production of the pro-inflammatory mediators IL-6 and TNF-a. The aim of the present study was to investigate which mechanisms underlie the up-regulation of the al-adranargic receptor, since PBMC of healthy individuals do not express al-adrenargic receptors. We used the human monocyUc cell-Une THP-1 as a model to study regulation of a~-adrenergic receptor expression, al-Adrenergic receptors compdse a heterogeneous family which can structurally and functionally be divided into three subtypes: a l a , a l b and a i d . mRNA levels for both the alb- and the aldadranergic receptor could be detected by RT-PCR in THP-1 cells whereas no cOa-adrenergic receptor signal was present. The glucocor~ceid dexamethasona as well as I~-adrenergio activation results in increased cob and ald-adranergio receptor mRNA. In addition, receptor protein levels as determined by Western blotting for the alb- and ald-adrenergic receptor increased. These results demonstrated that expression of al-adrenergic expression in monocytea can be regulated by neuroendocrine mediators.
To study the relationship between brain and immune activity, we compared positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) with peripheral measures of immune activity in 9 phobic and non-phobic volunteers. During PET-scan. subjects were exposed to a neutral videotape. Natural killer (NK) cell activity was associated with rCBF in the secondary sensory cortex (r = -,88; p<.01 at an effector to target cell ratio of 25:1). Proliferative responses to Con A were correlated with rCBF in the secondary sensory (r = .92; p<,01 for Con A 37.5 [tg/ml), secondary motor (r = .9g; p<.O01 for Con A 75 I.tg/mlLand secondary visual (r = .94; p<.O1 for Con A 75) areas. proliferative responses to Con A 75 were also associated with rCBF in the putamen and the thalamus (r = .94; p<.Ol and r = .89; p<.OI). In relation to immune parameters, no systematic effects of brain lateralization could be observed. The subjects were studied during resting conditions, and were free from infection. allergy or inflammation. Therefore, we suggest that the observed relations reflect trait-dependant factors common to brain and immune I~anctioning. In animal research, cortical areas have been indicated as playing a role in immune modulation. Through the use of brain imaging, the present study preliminary adds new evidence of a coupling between cortical brain areas, here shown predominantely in associative structures, and the immune system.
41
215 A-Adrenoreception in Experimental Meningoeoccal Intoxication
218 Antidepressants as Neuroimmunomodulators at Postreceptor Level
,I, Karpov, W. Sbeiti, A. Sampson, MinskMedicalInstitution,Belarus,A. Milutin,
H. Kovaru. Charles University,CzechRep., A. Fiserova, AcademyofScience, Czech Rep., A. Spnaova, Masaryk University,CzechRep., V. Lisa, Academyof Science, Czech Rep., Z. Fisar, CharlesUniversity,CzechRep, J. Velek, Academyof Science, CzechRep.
Minskgcological College,Belarus
Mcllingococcul lneningitls is often accompanied by tneningococeentia ;-lud infectious toxic shock. In correct trealmen! of such patients physician unlsl take illtU aco0unt IIw, stage i1[ adrenoreccption, which Call canse severe hypotonia "file expcritnc1|lzl Ineltingncoccu] intoxicatiun was t.odcll~:d wilh inlravenous injection of meningoc0ecal LPS to 12 rabbits 1400-16tl0g weight nndcr thc lighl ba~t~iraratic narcosis. The quantity of ~-adrtmorecepfurs in lencocylic mcuthranes was teste.d us'ing radioligalld mclhod. Tlle low tltt;,mlilynf tx-adrenore,ceptur$ was detected during file inloxicatiun. The lowest rate was in te,rlnlinal singes of itttnaicatlon 78,4 ./.15,6 fl,ol\mg (ccnlllul 3(14,5+_54,4 fmolhalg). "llles, the decrease of adrenoreception K~;one of the intporlaltt Inechanisms in contp]icaled menmgococeal infectinn and it should be taken into aecoonl dining early intensive care.
216 I-Iistiostrueture of the MRL-1 Miees Thymus, Spleen and Nonapcptidergie Centres of the Hypothalamus During Correction of Autoimmune Pathology A.A. Stadnikov, L.N. Shishkanova, ~ S.O. Mitryakov, A.M. Mikhailov, V.A. Valeev, L.A. Lepatinskaya, StateMedicaIAcademy,Russia
Were used 43 MBL-I mice, a~ed 3-5 monthes, with ~enetically determined autoimmune pathology. They were separated for ~roups de~endinff from the treatment. It included: dic~ofenac-natrium, interrupted adaptation for h y p o b a r i c hypoxia condition, and both of these methods. Material were studied by light-optical, electron microscopy and morphometry. Our investi[ation revealed some disordes of neurosecretory process at the nonapeptiderffic centres and obstruction of neuropeptides excretion to the blood. No one correction method have not significantly normalized cytophysiolo[ical processes in investi~ated orffans. More positive dynamic were noted in male mice, then female, especially usin~ both of diclofenac and baroadaptation.
Antidepressants can evoke alterations in cell signalling including hetcrotrimeric GTP-binding (G) proteins. We used rat C6 glioma cell Imc. C6 cells transfected (t) with pig thymus lymphocyte markers (MHC 11, CDd, pan T, etc)(1) and natural killer (NK) lymphocy'tes. We analyzed postreceptor effects ofsertraline. SEIL (Pfizer) flnoxeline, FLU, and mnclobemide, MOC. (Roche). We studied changes of Go. subumts (Gq/l 1, Gs, Gil.2) using ELISA and Western immunoblotting (2.3). MOC effects are linked to changes in Gots/Gcxil,2 as supported by our in vivo studies. We demonstrated FLU effects on decreased level ofC,mt q/l I in both C6- and human NK cells, in contrast t o (t)C6 cells regulated by Gas and G~ (i 1,2). We observed FLU induced Cax q/l I down regulation accompanied with lower IP3 level (PLC effector). SER effects were linked to adenylyl cyclase via Gets and purinoceptor (adenosine receptor) coupled G protein effects were not accompanied by, apoptosis, whereas FLU affected this pathway with subsequent apoptic evems. Ref.: l.Kovgff=et al. (this congress). 2. Kovm~t'tet aL Proe Royal MicnSoc., 1997.Pt2 : 123. 3.Kovfifflet al. Acta Vet.Brno. 1998.67 (accepted). Supportedby grants ofGA (~R 309/95/1121. GAUl( 143/97 and partially by Pf~er and R~x:heCo.
219 T h e Suppressive Effect of A n t i d e p r e s s a n t D r u g s on the I m m u n i t y of Stressed A n i m a l s M. Kubera, InstituteofPharmacologyPAS,Poland, V. Holan, Institute ofMolecular Genetics, CzechRep., A. Basta-Kaim, J. Borycz, A. Rum an, E. Nowak, Institute of
PharmacologyPAS,Poland
The study was aimed at examining the influence of single and repeated administration of antidepressant drags (amitriptyline, desipramine, fluoxetine and citalopram) in a dose of 10 mg/kg i.p. on the immunity of animals subjected respectively to a single swimming stress, or to a chronic action of mild stressor stimuli (an aminal model of depression). The immunity was assessed, among others, by the ability of splenocytes to proliferate and synthesize cytokines (ILq. II.,.-2, 11,-4, IL-6, IL-I0 and IFN--I). It was found that both single and chronic administration of the above-mentioned drugs to stressed animals induced a decrease in majority of parameters studied, whereas those drugs per se produced an opposite effect. The stress itself did not affect most of the paramours tested; however, in part of the chronically stressed animals a significant increase in IL-I synthesis was observed.
217
220
Neuroendocrine M e d i a t o r s U p r e g u l a t e o~l-Adrenergie Receptors
N e u r o - l m m u n e R e l a t i o n s h i p s Studied with P E T M. Lekander. KarolinskaHospital, Sweden, M. Fredrikson, UppsalaUniversity,
on Monocytes A. Kavelaars. C. Rouppe vd Voort, M. van de Pol, C.J. Heynen, UniversityChildren
Sweden,O. wik, Martin-Luther Universitaet,Germany
Hospital Utrecht,Netherlands
Children with Juvenile Chronic Arthritis have an aberrant response of the immune system to catecholamines. Peripheral blood mononuclear cells (PBMC) of these patients respond to at-adrenergic activation with an increased production of the pro-inflammatory mediators IL-6 and TNF-a. The aim of the present study was to investigate which mechanisms underlie the up-regulation of the al-adranargic receptor, since PBMC of healthy individuals do not express al-adrenargic receptors. We used the human monocyUc cell-Une THP-1 as a model to study regulation of a~-adrenergic receptor expression, al-Adrenergic receptors compdse a heterogeneous family which can structurally and functionally be divided into three subtypes: a l a , a l b and a i d . mRNA levels for both the alb- and the aldadranergic receptor could be detected by RT-PCR in THP-1 cells whereas no cOa-adrenergic receptor signal was present. The glucocor~ceid dexamethasona as well as I~-adrenergio activation results in increased cob and ald-adranergio receptor mRNA. In addition, receptor protein levels as determined by Western blotting for the alb- and ald-adrenergic receptor increased. These results demonstrated that expression of al-adrenergic expression in monocytea can be regulated by neuroendocrine mediators.
To study the relationship between brain and immune activity, we compared positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) with peripheral measures of immune activity in 9 phobic and non-phobic volunteers. During PET-scan. subjects were exposed to a neutral videotape. Natural killer (NK) cell activity was associated with rCBF in the secondary sensory cortex (r = -,88; p<.01 at an effector to target cell ratio of 25:1). Proliferative responses to Con A were correlated with rCBF in the secondary sensory (r = .92; p<,01 for Con A 37.5 [tg/ml), secondary motor (r = .9g; p<.O01 for Con A 75 I.tg/mlLand secondary visual (r = .94; p<.O1 for Con A 75) areas. proliferative responses to Con A 75 were also associated with rCBF in the putamen and the thalamus (r = .94; p<.Ol and r = .89; p<.OI). In relation to immune parameters, no systematic effects of brain lateralization could be observed. The subjects were studied during resting conditions, and were free from infection. allergy or inflammation. Therefore, we suggest that the observed relations reflect trait-dependant factors common to brain and immune I~anctioning. In animal research, cortical areas have been indicated as playing a role in immune modulation. Through the use of brain imaging, the present study preliminary adds new evidence of a coupling between cortical brain areas, here shown predominantely in associative structures, and the immune system.