Studies of the Systemic Inflammation in Psoriasis

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Studies of the Systemic Inflammation in Psoriasis

Sigurdardottir, Gunnthorunn, 1975- (författare): Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten

Enerbäck, Charlotta, 1965- (preses): Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland

Bivik, Cecilia, 1978- (preses): Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten

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Synnerstad, Ingrid, 1968- (preses): Linköpings universitet,Medicinska fakulteten

Bradley, Maria, Docent (opponent): Karolinska Institutet, Stockholm, Sweden

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ISBN 9789176852569
Linköping : Linköping University Electronic Press, 2018
Engelska 93 s.
Serie: Linköping University Medical Dissertations, 0345-0082 ; 1632

Relaterad länk:: https://doi.org/10.3...; visa fler...; https://liu.diva-por... (primary) (Raw object); https://liu.diva-por...; https://liu.diva-por... (Preview); http://liu.diva-port...; https://urn.kb.se/re...; https://doi.org/10.3...; visa färre...

Doktorsavhandling (övrigt vetenskapligt/konstnärligt)

Abstract Ämnesord

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Psoriasis is a common immune-mediated disease, where an increased prevalence of extra cutaneous diseases and mortality is observed. Common inflammatory mechanisms are implicated. The general aim of this thesis was to investigate markers of inflammation and cardiovascular disease in psoriasis, now considered a systemic disease, assumed to reflect the systemic inflammation.In Study I, Th1-, Th2- and Th17-associated chemokines were elevated in the blood of psoriasis patients in comparison to controls and, in Study II, six markers of cardiovascular risk were demonstrated to be systemically elevated. After adjustment for body mass index and waist: hip ratio in Study II, only one marker, the total plasminogen activator inhibitor-1, showed sustained elevated levels. The levels of the chemokines and the cardiovascular markers were unaffected after treatment with narrowband UVB therapy (NB-UVB), despite a significant improvement in skin lesions, indicating more local than systemic effects of NBUVB. This was further strengthened by the fact that the response to in-vitro stimulation in the peripheral blood mononuclear cells (PBMCs) of psoriasis patients before and after NB-UVB treatment was unaffected. In Study I, CCL20 was shown to correlate to the psoriasis area severity index (PASI), but this correlation was lost after phototherapy, suggesting sources of CCL20 other than the skin. Conversely, systemic treatment with TNF-α inhibition in Study II alleviated the elevated systemic levels of the cardiovascular risk markers. In Study III, the levels of 17 potential biomarkers, with the emphasis on endothelial and adipocyte dysfunction, soluble receptors and the innate mechanisms were studied. Endocan-1, CXCL16, and sVEGFR1, were found to be systemically decreased in psoriasis patients at baseline. Endocan-1 showed a negative correlation to the PASI. In contrast to the results in Studies I and II, NB-UVB therapy affected the systemic levels of investigated markers; Endocan-1 and CXCL16 were restored to normal levels, while sVEGF1, FABP3, FABP4 and sIL-1R1 showed a significant reduction following NB-UVB. In Study IV, the focus was on the contribution of innate immune mechanisms and the effects of the cytokines IL-17 and TNF-α on systemic inflammation. In keratinocytes, the gene and protein expression of inflammasome components was increased upon exposure to IL-17 and TNF-α. Systemically, the constitutive expression of the inflammasome components NLRP1, NLRP3 and AIM2 was detected in neutrophils, classical monocytes, CD4+ lymphocytes and B-cell subsets from psoriasis patients. Upon exposure to IL-17 and TNF-α, increased systemic caspase-1 levels were detected, confirming systemic inflammasome activity.In conclusion, these studies support the hypothesis that there is a systemic inflammation in psoriasis to which both innate and adaptive immune mechanisms contribute. The systemic inflammation may be explained, to some extent, but not completely, by body weight and fat distribution. The different effects of NB-UVB therapy on the systemic levels of the investigated markers may reflect their different roles in psoriasis, but the ameliorating effects of the TNF-α inhibitor on the elevated cardiovascular markers suggests that systemic treatment should be evaluated in psoriasis patients with signs of a systemic inflammatory burden.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

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Av författaren/redakt...: Sigurdardottir, ...; Enerbäck, Charlo ...; Bivik, Cecilia, ...; Synnerstad, Ingr ...; Bradley, Maria, ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Dermatologi och ...

Delar i serien: Linköping Univer ...

Av lärosätet: Linköpings universitet

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