no slide title · the end-points induced clearin-vivo immune response. acute immune response zcla...
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Human study
Immune modulationMarianne O’ Shea
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Content
Introduction: CLA and immune modulation
ObjectiveStudy designStudy parametersresultsConclusions
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CLA: Immune modulator
Immune disbalance
Chronic-/ acute inflammationAllergy– Humoral IR
– Antibody: IgE↓– Histamine ↓
Infection– Humoral IR
Antibodies– IL1, PGE2
Immune disbalance
Infection model: VaccinationSpecific
Immune response
– Humoral IRAntibodies
– Cellular IRDTH
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Specific immune systemHumoral immunity
Cellular immunity
Virus infected cell
Antigens
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Role APC in Th cell function
ThNAPC2
ThNAPC1
sentinelAPC
Th1IFN-γTNF-βIL-2
IL-4IL-13IL-5
pathogens
Th2
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cAMP upregulators
IL-12
ICAM-1
OX40L
sentinel APC APC0
APC1
APC2
Thn
Thn
Thn
Th1Th1
Th2
Th0
Type 0 factorsIL-1β/TNF-α
LPSSAC
Type 1 factorsbacteria
viruses
Type 2 factors
cholera toxinPGE2
histamine
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Objective
Treatment– 50:50 c9, t11-CLA : t10, c12-CLA– 80:20 c9, t11-CLA : t10, c12-CLA– Placebo - high oleic sunflower oil (HOSF)
Human– Humoral immune response– DTH (Delayed type hypersensitivity) reaction
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Study Design
Study designRandomised, parallel, double-blind trial
Infection ModelVaccination (Hepatitis B)
50:50
ctr01 03
80:20
57 7143
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Study Design
75 Subjects– 50:50 (3 g CLA/d)– 80:20 (3 g CLA/d)– Placebo (3 g HOSF/d)
13 week duration– Staggered start over 3 cohorts
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Main Dynamic Immunological Parameters
Examination of a specific immune response1. (DTH) recall antigens involves memory:
existing T-cells2.(Anti-Hb) Active immune response :
T-helper cellsB-cellsSpecific Antibodies
II Additional dynamic parameters3. CLA composition of white blood cells
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1. Delayed-Type Hypersensitivity
Cell-mediated immune responseMinor dose under skin– Tetanus, Diphteria,Tuberculin, Streptococcus,
Candida (albicans), Proteus (mirabilis),Trichophyton (mentagrophytes)
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2. Anti-Hepatitis B
Vaccinated (Serum anti HB antigen titres) – pre study– wk 11– wk 13
2 weeks post vaccination– anti HBs antibodies
determined
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1. Anti-Hepatitis B
Enzyme
Chromogen
• Sensitise plate with antigen
• Wash
• Add test antibody
• Wash
• Add ligand
• Wash
• Add chromogen
• Develop plate
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Results 1
Seroprotection rate– CLA 50:50 is 62.5%– CLA 80:20 is 36.4%– Ctr is 33.3%
Conclusion– 50:50 CLA enhanced the active humoral immune
response (antibody production)– CLA has a positive effect on the specific immune
system in humans
p=0.05ns
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Results 2
DTH (recall Ag’s):– Within normal range (start, end)– No stat.sign. differences between groups
Conclusion– CLA did not affect existing cellular immune
responses
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Conclusion
FA composition of PBMC: – total CLA ↑
CLA did not affect existing cellular immune responses
Seroprotection rate between CLA 50:50 group andcontrols enhanced (P=0.05).
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Conclusions I
The end-points induced clear in-vivo immune response.
Acute immune response
CLA 50:50 significantly increases the number of responders for antibody production and antigen specific proliferation of lymphocytes.
CLA 80:20 did no show any significant effect.
Seroprotection rate between CLA 50:50 group andcontrols was significant higher (P=0.05).
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Conclusions II
Memory immune response:
CLA had no significant effect on ex vivo mitogen (PHA) induced proliferation
CLA had no effect on existing cellular responsesas measured by the DTH reaction (existing T cell respons
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Acknowledgment
Loders Croklaan:Victoria Taran
Inge Mohede
Unilever Health Institute:ResistanceRuud AlbersReggy van der Wielen
TNO, food and nutritionresearch center, The NetherlandsLisette BrinkHenk Hendriks