SlideShare a Scribd company logo

More Related Content

What's hot (13)

Esv2n15
Esv2n15Esv2n15
Esv2n15
 
243 b cell
243 b cell243 b cell
243 b cell
 
Autoimmune disease
Autoimmune diseaseAutoimmune disease
Autoimmune disease
 
Atherosclerosis an autoimmune disease
Atherosclerosis an autoimmune diseaseAtherosclerosis an autoimmune disease
Atherosclerosis an autoimmune disease
 
Atherosclerosis, an autoimmune disease 2
Atherosclerosis, an autoimmune disease 2Atherosclerosis, an autoimmune disease 2
Atherosclerosis, an autoimmune disease 2
 
kayleighreport2014
kayleighreport2014kayleighreport2014
kayleighreport2014
 
Aeha multipeptide and passive
Aeha multipeptide and passiveAeha multipeptide and passive
Aeha multipeptide and passive
 
Atherosclerosis an autoimmune disease
Atherosclerosis  an autoimmune diseaseAtherosclerosis  an autoimmune disease
Atherosclerosis an autoimmune disease
 
501 autoimmune disease
501 autoimmune disease501 autoimmune disease
501 autoimmune disease
 
06 rencontres biomédicale LIR A Tedgui
06 rencontres biomédicale LIR A Tedgui06 rencontres biomédicale LIR A Tedgui
06 rencontres biomédicale LIR A Tedgui
 
074 influenza infection effects
074 influenza infection effects074 influenza infection effects
074 influenza infection effects
 
Immunità acquisita nelle IBD
Immunità acquisita nelle IBDImmunità acquisita nelle IBD
Immunità acquisita nelle IBD
 
Drnaghavi
DrnaghaviDrnaghavi
Drnaghavi
 

Viewers also liked

Kbj stock verification
Kbj stock verificationKbj stock verification
Kbj stock verificationpratapbarik
 
Educación virtual Valentín castro
Educación virtual Valentín castro Educación virtual Valentín castro
Educación virtual Valentín castro valecastro27
 
LIGHTING by Keyani
LIGHTING by KeyaniLIGHTING by Keyani
LIGHTING by Keyanishahzad raki
 
Leyendo y escribiendo con tics aprendo y me
Leyendo y escribiendo con tics aprendo y meLeyendo y escribiendo con tics aprendo y me
Leyendo y escribiendo con tics aprendo y mecarmenxitacruz
 
Crear Cuenta Gmail
Crear Cuenta GmailCrear Cuenta Gmail
Crear Cuenta Gmailguest550e3e
 
Complementary Professions? Occupational Therapy and Occupational Health in t...
Complementary Professions?  Occupational Therapy and Occupational Health in t...Complementary Professions?  Occupational Therapy and Occupational Health in t...
Complementary Professions? Occupational Therapy and Occupational Health in t...Royal College of Occupational Therapists
 
Product Testimonials
Product TestimonialsProduct Testimonials
Product Testimonialsslevin0711
 
DiseñO De Reactores
DiseñO De ReactoresDiseñO De Reactores
DiseñO De Reactoresguest5b8055
 
Prognostic Indicators and Outcome Measures_4-5
Prognostic Indicators and Outcome Measures_4-5Prognostic Indicators and Outcome Measures_4-5
Prognostic Indicators and Outcome Measures_4-5Michelle Sheridan
 
Hybrid - Official Business Presentation
Hybrid - Official Business PresentationHybrid - Official Business Presentation
Hybrid - Official Business PresentationRaymond Red
 
Cybercrime Awareness Campaign
Cybercrime Awareness CampaignCybercrime Awareness Campaign
Cybercrime Awareness CampaignJessica Anandajoo
 
Principles of use of plaster of paris
Principles of use of plaster of parisPrinciples of use of plaster of paris
Principles of use of plaster of parisAsi-oqua Bassey
 
8 steps for excellent B2B CX (customer experience)
8 steps for excellent B2B CX (customer experience)8 steps for excellent B2B CX (customer experience)
8 steps for excellent B2B CX (customer experience)B2B Marketing
 

Viewers also liked (19)

The prev of inf cells in nonrupt a. plaque pasterkamp- part 2
The prev of inf cells in nonrupt a. plaque  pasterkamp- part 2The prev of inf cells in nonrupt a. plaque  pasterkamp- part 2
The prev of inf cells in nonrupt a. plaque pasterkamp- part 2
 
BLS card
BLS cardBLS card
BLS card
 
Flujo de conserva natural
Flujo de conserva naturalFlujo de conserva natural
Flujo de conserva natural
 
Kbj stock verification
Kbj stock verificationKbj stock verification
Kbj stock verification
 
Educación virtual Valentín castro
Educación virtual Valentín castro Educación virtual Valentín castro
Educación virtual Valentín castro
 
DEBER 2
DEBER 2DEBER 2
DEBER 2
 
LIGHTING by Keyani
LIGHTING by KeyaniLIGHTING by Keyani
LIGHTING by Keyani
 
Leyendo y escribiendo con tics aprendo y me
Leyendo y escribiendo con tics aprendo y meLeyendo y escribiendo con tics aprendo y me
Leyendo y escribiendo con tics aprendo y me
 
Crear Cuenta Gmail
Crear Cuenta GmailCrear Cuenta Gmail
Crear Cuenta Gmail
 
Complementary Professions? Occupational Therapy and Occupational Health in t...
Complementary Professions?  Occupational Therapy and Occupational Health in t...Complementary Professions?  Occupational Therapy and Occupational Health in t...
Complementary Professions? Occupational Therapy and Occupational Health in t...
 
Product Testimonials
Product TestimonialsProduct Testimonials
Product Testimonials
 
DiseñO De Reactores
DiseñO De ReactoresDiseñO De Reactores
DiseñO De Reactores
 
Support Dementia: using wearable assistive technology and analysing real-time...
Support Dementia: using wearable assistive technology and analysing real-time...Support Dementia: using wearable assistive technology and analysing real-time...
Support Dementia: using wearable assistive technology and analysing real-time...
 
Royale Business Club
Royale Business ClubRoyale Business Club
Royale Business Club
 
Prognostic Indicators and Outcome Measures_4-5
Prognostic Indicators and Outcome Measures_4-5Prognostic Indicators and Outcome Measures_4-5
Prognostic Indicators and Outcome Measures_4-5
 
Hybrid - Official Business Presentation
Hybrid - Official Business PresentationHybrid - Official Business Presentation
Hybrid - Official Business Presentation
 
Cybercrime Awareness Campaign
Cybercrime Awareness CampaignCybercrime Awareness Campaign
Cybercrime Awareness Campaign
 
Principles of use of plaster of paris
Principles of use of plaster of parisPrinciples of use of plaster of paris
Principles of use of plaster of paris
 
8 steps for excellent B2B CX (customer experience)
8 steps for excellent B2B CX (customer experience)8 steps for excellent B2B CX (customer experience)
8 steps for excellent B2B CX (customer experience)
 

Similar to Towards immune modulation vp (20)

178 vaccination against atherosclerosis
178 vaccination against atherosclerosis178 vaccination against atherosclerosis
178 vaccination against atherosclerosis
 
189 hsp 65
189 hsp 65189 hsp 65
189 hsp 65
 
Mark A. Atkinson
Mark A. AtkinsonMark A. Atkinson
Mark A. Atkinson
 
Immunotherapy Web Presentation
Immunotherapy   Web PresentationImmunotherapy   Web Presentation
Immunotherapy Web Presentation
 
Drugs acting on the immune system
Drugs acting on the immune systemDrugs acting on the immune system
Drugs acting on the immune system
 
inflammation in mice.pdf
inflammation in mice.pdfinflammation in mice.pdf
inflammation in mice.pdf
 
Immunology 1, 2, 3
Immunology 1, 2, 3Immunology 1, 2, 3
Immunology 1, 2, 3
 
State of Lupus Treatment: New Therapeutics
State of Lupus Treatment: New TherapeuticsState of Lupus Treatment: New Therapeutics
State of Lupus Treatment: New Therapeutics
 
07. immunology
07. immunology07. immunology
07. immunology
 
238570.pptx
238570.pptx238570.pptx
238570.pptx
 
Understanding immunology for internists 1
Understanding immunology for internists   1Understanding immunology for internists   1
Understanding immunology for internists 1
 
Ferretti et al., BBI 2016
Ferretti et al., BBI 2016Ferretti et al., BBI 2016
Ferretti et al., BBI 2016
 
Common variable immunodeficiency 2017
Common variable immunodeficiency 2017Common variable immunodeficiency 2017
Common variable immunodeficiency 2017
 
Harats
HaratsHarats
Harats
 
242 lipid lowering
242 lipid lowering242 lipid lowering
242 lipid lowering
 
242 lipid lowering
242 lipid lowering242 lipid lowering
242 lipid lowering
 
Esv2n37 b
Esv2n37 bEsv2n37 b
Esv2n37 b
 
Immunosenescence
ImmunosenescenceImmunosenescence
Immunosenescence
 
243 b cell
243 b cell243 b cell
243 b cell
 
Cellular Adhesion in Inflammation
Cellular Adhesion in InflammationCellular Adhesion in Inflammation
Cellular Adhesion in Inflammation
 

More from Society for Heart Attack Prevention and Eradication

More from Society for Heart Attack Prevention and Eradication (20)

AHA SHAPE Symposium 2017 Dr. Naghavi Presentation
AHA SHAPE Symposium 2017 Dr. Naghavi PresentationAHA SHAPE Symposium 2017 Dr. Naghavi Presentation
AHA SHAPE Symposium 2017 Dr. Naghavi Presentation
 
AHA SHAPE Symposium 2017 Dr. Kloner Presentation
AHA SHAPE Symposium 2017 Dr. Kloner PresentationAHA SHAPE Symposium 2017 Dr. Kloner Presentation
AHA SHAPE Symposium 2017 Dr. Kloner Presentation
 
AHA SHAPE Symposium 2017 Dr. Greenland Presentation
AHA SHAPE Symposium 2017 Dr. Greenland PresentationAHA SHAPE Symposium 2017 Dr. Greenland Presentation
AHA SHAPE Symposium 2017 Dr. Greenland Presentation
 
AHA SHAPE Symposium 2017 Dr. Yen Presentation
AHA SHAPE Symposium 2017 Dr. Yen PresentationAHA SHAPE Symposium 2017 Dr. Yen Presentation
AHA SHAPE Symposium 2017 Dr. Yen Presentation
 
AHA SHAPE Symposium 2017 Dr. Slomka Presentation
AHA SHAPE Symposium 2017 Dr. Slomka PresentationAHA SHAPE Symposium 2017 Dr. Slomka Presentation
AHA SHAPE Symposium 2017 Dr. Slomka Presentation
 
Vu lplaque1 pasterkamp
Vu lplaque1 pasterkampVu lplaque1 pasterkamp
Vu lplaque1 pasterkamp
 
Vulnerable plaque vulnerable patient
Vulnerable plaque vulnerable patientVulnerable plaque vulnerable patient
Vulnerable plaque vulnerable patient
 
Vulnerable plaque overview
Vulnerable plaque overviewVulnerable plaque overview
Vulnerable plaque overview
 
Vulnerable patient talk in poland
Vulnerable patient talk in polandVulnerable patient talk in poland
Vulnerable patient talk in poland
 
Vulnerable patient slides without movies
Vulnerable patient slides without moviesVulnerable patient slides without movies
Vulnerable patient slides without movies
 
Vulnerable patient mar 04
Vulnerable patient mar 04Vulnerable patient mar 04
Vulnerable patient mar 04
 
Vulnerable (thrombogenic blood
Vulnerable (thrombogenic bloodVulnerable (thrombogenic blood
Vulnerable (thrombogenic blood
 
Vuln shape aha 2005
Vuln shape aha 2005Vuln shape aha 2005
Vuln shape aha 2005
 
Vuln plaque poster burke
Vuln plaque poster burkeVuln plaque poster burke
Vuln plaque poster burke
 
Vp watch editorial_slide 25short-
Vp watch editorial_slide 25short-Vp watch editorial_slide 25short-
Vp watch editorial_slide 25short-
 
Vp watch editorial_slide25
Vp watch editorial_slide25Vp watch editorial_slide25
Vp watch editorial_slide25
 
Vp watch editorial_slide25short-
Vp watch editorial_slide25short-Vp watch editorial_slide25short-
Vp watch editorial_slide25short-
 
Vp watch2002
Vp watch2002Vp watch2002
Vp watch2002
 
Vp symposium31602
Vp symposium31602Vp symposium31602
Vp symposium31602
 
Vpschoenhagen
VpschoenhagenVpschoenhagen
Vpschoenhagen
 

Recently uploaded

bleeding disorders 1 Dr.Nannika Pradhan
bleeding disorders 1  Dr.Nannika Pradhanbleeding disorders 1  Dr.Nannika Pradhan
bleeding disorders 1 Dr.Nannika Pradhanthesalberry
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsPradnya Wadekar
 
Thyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersThyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersSai Sailesh Kumar Goothy
 
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Dr. Dheeraj Kumar
 
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfEMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfMayuriGamit2
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomSudhir Kumar
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)chahattyagi200
 
Ovarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxOvarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxSizan Thapa
 
Substance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionSubstance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionZeinabEmad3
 
The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...JakeMatthews12
 
Basic of Thyroid Hormone:- An In-depth Analysis
Basic of Thyroid Hormone:- An In-depth AnalysisBasic of Thyroid Hormone:- An In-depth Analysis
Basic of Thyroid Hormone:- An In-depth AnalysisAshishMaletha2
 
Ayurveda research in Hypothyroidism, P
Ayurveda  research  in Hypothyroidism, PAyurveda  research  in Hypothyroidism, P
Ayurveda research in Hypothyroidism, PDr.Shalu Jain
 
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptx
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptxANATOMY OF CEREBELLUM With Clinical Anatomy.pptx
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptxsiddharthroy26587
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeQuick MedTalk
 
SGK PHÙ PHỔI CẤP ĐHYHN .pdf
SGK PHÙ PHỔI CẤP ĐHYHN                   .pdfSGK PHÙ PHỔI CẤP ĐHYHN                   .pdf
SGK PHÙ PHỔI CẤP ĐHYHN .pdfHongBiThi1
 
Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......anupamdas2143
 
TARGET DELINEATION IN CERVIX CANCER BY DR KANHU
TARGET DELINEATION IN CERVIX CANCER BY DR KANHUTARGET DELINEATION IN CERVIX CANCER BY DR KANHU
TARGET DELINEATION IN CERVIX CANCER BY DR KANHUKanhu Charan
 

Recently uploaded (20)

bleeding disorders 1 Dr.Nannika Pradhan
bleeding disorders 1  Dr.Nannika Pradhanbleeding disorders 1  Dr.Nannika Pradhan
bleeding disorders 1 Dr.Nannika Pradhan
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractions
 
Thyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersThyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disorders
 
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
 
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfEMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)
 
Ovarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptxOvarian tumors Lecture notes for MBBS.pptx
Ovarian tumors Lecture notes for MBBS.pptx
 
Substance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), AddictionSubstance use disorder (drug addict ), Addiction
Substance use disorder (drug addict ), Addiction
 
The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...
 
Basic of Thyroid Hormone:- An In-depth Analysis
Basic of Thyroid Hormone:- An In-depth AnalysisBasic of Thyroid Hormone:- An In-depth Analysis
Basic of Thyroid Hormone:- An In-depth Analysis
 
Ayurveda research in Hypothyroidism, P
Ayurveda  research  in Hypothyroidism, PAyurveda  research  in Hypothyroidism, P
Ayurveda research in Hypothyroidism, P
 
Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
 
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
Catalysts for Change in SCLC: Optimizing the Use of Standard Therapies and Ac...
 
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptx
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptxANATOMY OF CEREBELLUM With Clinical Anatomy.pptx
ANATOMY OF CEREBELLUM With Clinical Anatomy.pptx
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
 
Oral disorders .pptx
Oral disorders .pptxOral disorders .pptx
Oral disorders .pptx
 
SGK PHÙ PHỔI CẤP ĐHYHN .pdf
SGK PHÙ PHỔI CẤP ĐHYHN                   .pdfSGK PHÙ PHỔI CẤP ĐHYHN                   .pdf
SGK PHÙ PHỔI CẤP ĐHYHN .pdf
 
Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......
 
TARGET DELINEATION IN CERVIX CANCER BY DR KANHU
TARGET DELINEATION IN CERVIX CANCER BY DR KANHUTARGET DELINEATION IN CERVIX CANCER BY DR KANHU
TARGET DELINEATION IN CERVIX CANCER BY DR KANHU
 

Towards immune modulation vp

  • 1. Towards Immune Modulation against Vulnerable Plaque Göran K Hansson Center for Molecular Medicine Karolinska Institutet Stockholm, Sweden Vulnerable Plaque Symposium Chicago, IL, November 2002
  • 2. Hansson, Libby, Schönbeck & Yan, Circ Res 2002
  • 3. Potential targets for immunomodulation of atherosclerosis • Specific antigens – oxLDL, HSP65, β2GpI, microbial • C pneum, CMV, others • Co-stimulatory molecules – CD40/CD40L, CD28/B7 • Cytokines – IFNγ, TNFα (aggravating) – IL-10, TGFβ (protective) • Vaccines • Recombinant proteins • Antibodies • Cells • Small molecule drugs
  • 4. Atherosclerosis in the absence of adaptive immunity? (G K Hansson & J Nilsson, in: Crawford & DiMarco, Cardiology)
  • 5. CD4+ T cells aggravate atherosclerosis in immunodeficient apoExSCID mice * ApoE- SCID ApoE- T and B cells No CD4+ T Yes transfer Aortic lesion size Zhou, Nicoletti, Elhage & Hansson Circ 102:2919 2000 ApoE- SCID
  • 6. Immunosuppression to reduce CD4+ T cell activity? • General immunosuppression is likely to reduce atherosclerosis – Some support from animal studies • But substantial side effects – Infections – Direct vascular effects of drugs • Therefore, general immunosuppression is unlikely to be used to treat atherosclerosis or even vulnerable plaque
  • 7. Complexity of immune regulatory networks • Counterbalancing cell subsets • Idiotypic antibody networks • Regulatory cytokines
  • 8. The Th1/Th2 Paradigm Th IL-12 MHC Peptide TCRTCR IFN-γ IL-18 Th1 IFN-γ MΦ IFN-γ B Ab DTH InflammationAPC APC Th IL-4 Th2Th2 B IL-3, 5 IL-4 IL-10 IL-13 - IL-4, 10, 13 Antibodies Allergy
  • 9. Hypothesis: Th1/Th2 balance controls atherosclerosis – Th1 cells dominate in lesions and are proatherogenic • CD4+ Th1 cells (Hansson 89; Uyemura 96; Frostegård 99) • Interferon-γ, TNF-α; IL-12, IL-18 (Zhou 00; Mallat 01; Daugherty 01) –Th2 cytokines that inhibit Th1 may be antiatherogenic? – IL-10-/- B6 mice develop larger fatty streaks – IL-10 administration reduces disease » Mallat et al; Pinderski et al. 99
  • 10. Increased atherosclerosis in IL-10 deficient apoE-/- mice IL10-/- E-/- IL10+/+ E-/- Caligiuri, Hansson, Rudling, Michel, Nicoletti 2002 * 100 50 Lesion size (x 103 µm2) in 16 wks old mice
  • 11. Antiatherosclerotic cytokines - useful for therapy? • Powerful, direct approach • Recombinant cytokines available • But these cytokines are usually immunosuppressive / antiinflammatory, therefore – Increased sensitivity to infections – Cytokine-specific side effects • E.g. TGFβ – fibrosis • Therefore, these cytokines might be useful in acute coronary syndromes, • although not in chronic atherosclerosis
  • 12. Inflammation Repair Innate immunity / TLRs Adaptive Th1 immunity IFN-γ TNF-α, IL-1 Inhibitory cytokines Cells? IL-10 TGF-β Ab? Accelerated athero Plaque activation Reduced athero Stable plaque Silent disease Immune regulation of plaque activity
  • 13. B cells of atherosclerotic mice carry atheroprotective immunity 0 50 100 150 200 250 Sham Sx Sx Sx Transfer - - T B * * ‡ ‡ Lesionsize Caligiuri et al, JCI 109:745, 2002 ApoE mice Sx, trf 6 wk age Analysis 18 wk
  • 14. Atheroprotective immunity • Carried by spleen B cells • Reduces lesion size and stage • Reduces CD4+ T cell infiltration in lesions • Correlates with anti-oxLDL antibodies • Protective effect of antibodies? – Clearance of oxLDL?
  • 15. Protective immunity against atherosclerosis • Can we induce it by immunization? • A vaccination strategy against atherosclerosis?
  • 16. Protective immunization 1. Oxidized LDL Parenteral immunization (sc) Model: Mutant rabbits, mice Antigen: OxLDL, MDA-LDL Freund´s adjuvant Repeated inj 3 wk intervals Significant protection after 3 months! Palinski PNAS 95; Ameli ATVB 96; George Athero 99; Zhou ATVB 00
  • 17. MDA-LDL ”vaccination” reduces atherosclerosis Immunogen (PBS) Plaque MDA-LDL extract ApoE-/- mice Immun wk 6 / FCA Boost wk 8,10,12,14 Analysis wk 18 Zhou et al, ATVB 2000
  • 18. Protective immunization 2. Heat shock protein 65/60 • HSP60 released upon cell injury and in atherosclerosis – Wick, Xu et al. 1992 • HSP65/60 X-reacts man-microbe • Mucosal administration of HSP65 – Nasal, oral • Reduced lesions in LDLR mice – Maron, Libby, Weiner, Circ 2002 – Harats, Shoenfeld, George, JACC 2002
  • 19. Inflammation Repair Innate immunity / TLRs Adaptive Th1 immunity IFN-γ TNF-α, IL-1 Inhibitory cytokines Protective B cells IL-10 TGF-β Ab? MΦ activation Endothelial activation Radicals Proteinases Prothrombotic state Antiinflammation Fibrosis SMC proliferation Antibody clearance Immune regulation of plaque activity Vaccine
  • 20. Small molecule drugs that modulate athero-immunity • Pentoxifyllin – Inhibits Th1 immune responses – Inhibits atherosclerosis in mice • Laurat et al Circ 2001 • Statins – Inhibit Th1 responses! • Kwak Nat Med 2000; Youssef Nature 2002 – Inhibit atherosclerosis in mice and men
  • 21. Statins inhibit Th1 immunity • Downregulate interferon-γ induced HLA-II transcription in macrophages – Kwak, Mach et al, Nature Med 2000 • Inhibit Th1 signalling • Increase Th2 cytokines • Inhibit autoimmune encephalomyelitis – Youssef, Steinman et al, Nature 2002
  • 22. Inflammation Repair Innate immunity / TLRs Adaptive Th1 immunity IFN-γ TNF-α, IL-1 Inhibitory cytokines Protective B cells IL-10 TGF-β Ab MΦ activation Endothelial activation Radicals Proteinases Prothrombotic state Antiinflammation Fibrosis SMC proliferation Antibody clearance Immune modulation of vulnerable plaque Vaccines Drugs