Dual role of IL-12 in the therapeutic efficacy or failure ... role of IL-12... · T0 T4 T12 T24 0...

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Transcript of Dual role of IL-12 in the therapeutic efficacy or failure ... role of IL-12... · T0 T4 T12 T24 0...

  • 0

    3

    6

    0

    3

    6 ***

    IL-6

    NI HCV NT

    0

    12

    24

    CT HCV - NT

    0

    12

    24

    ***

    IL-10

    0

    250

    500

    0

    250

    500

    IL-12

    0

    10

    20

    0

    10

    20

    ***

    TNF-αγ

    0

    15

    30

    0

    15

    30

    IFN-

    [pg/m

    L]

    0

    50

    100

    0

    50

    100 ***

    IL-8

    [pg

    /mL]

    NI HCV NT

    0

    10

    20

    CT

    HCV - NT

    0

    10

    20 **

    IL-4

    [pg/m

    L]

    CYTOKINE PROFILE Legend

  • T0 T4 T12 T24

    100

    102

    104

    106

    108

  • IL-8 IL-6 IL-12TNF-α

    IFN-γ

    T0 T4 T12 T24

    IL-4

    T0 T4 T12 T24

    IL-10

    T0 T4 T12 T24

    PAIRED CYTOKINE PROFILES

    Time after Treatment

    Se

    rum

    Le

    ve

    l[p

    g/m

    L]

    T0 T4 T12 T24

    PAIRED VIRAL LOAD

    HCV - SVR

    HCV - NR

    100

    104

    108

    Vire

    mia

    [IU

    /mL]

    Cut-off – 200 IU/mL

    Mean CT = 33

    Mean CT = 0.1

    Mean CT = 95

    Mean CT = 0.1

    Mean CT = 3.5

    B C ED

    F G H

    A

    0

    10

    20

    0

    20

    40

    0

    13

    26

    0

    150

    300

    0

    7

    14

    0

    5

    10

    0

    5

    10

    Mean CT = 0.6Mean CT = 1.2

  • 0

    200

    400

    600

    800

    0

    70

    140

    0

    200

    400

    600

    800

    0

    70

    140

    T4/T0

    Time Ratio

    T12/T0 T24/T0 T4/T0 T12/T0 T24/T0

    Ba

    selin

    e F

    old

    Change

    HCV - SVR HCV - NR

    CHANGES IN THE BASELINE CYTOKINE PATTERN

    IL-8 IL-6

    IL-12

    TNF-α

    IFN-γ

    IL-4

    IL-10

    IL-8

    IL-6

    IL-12

    TNF-α

    IFN-γ

    IL-4

    IL-10

    A B

  • 0

    30

    60 >T0 >T0

    * *

    0

    15

    30

    T0,>T24

    T0 T4 T12 T240

    7

    14

    *

    *

    *

    *

    >T0>T0

    >T0

    0

    30

    60* *

    0

    15

    30

    0.0

    1.5

    3.0

    T0 T4 T12 T240

    13

    26

    **

    *

    *

    T0 T4 T12 T240

    7

    14*

    **

    *

    Fre

    quency o

    f G

    ate

    d C

    ells

    (%

    )

    CD69+ Monocytes

    Time after Treatment

    Time after Treatment

    % o

    f gate

    d lym

    phocyte

    s

    Cell

    Ratio

    Fre

    quency o

    f G

    ate

    d C

    ells

    (%

    )

    CD69+ Lymphocytes

    CD4+ T-cells CD8+ T-cells CD4+/CD8+ T-cell Ratio

    Fre

    quency o

    f G

    ate

    d C

    ells

    (%

    )

    CD69+ Monocytes

    % o

    f gate

    d lym

    phocyte

    s

    Cell

    Ratio

    CD69+ Lymphocytes

    CD4+ T-cells CD8+ T-cells CD4+/CD8+ T-cell Ratio

    Fre

    quency o

    f G

    ate

    d C

    ells

    (%

    )HCV-SVR

    HCV-N

    R

    CELL SUBSETS AND ACTIVATION STATUS

    A

    B