Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass...

ORIGINAL ARTICLE

Circulating adipokine levels in Portuguese patients withpsoriasis vulgaris according to body mass index, severityand therapy

S Coimbra,†,‡,§,* H Oliveira,– F Reis,†† L Belo,†,‡ S Rocha,†,‡ A Quintanilha,‡,‡‡ A Figueiredo,–

F Teixeira,†† E Castro,†,‡ P Rocha-Pereira,‡,§§ A Santos-Silva†,‡

†Faculdade de Farmacia, Servico de Bioquımica, Universidade do Porto, Porto, ‡Instituto de Biologia Molecular e Celular (IBMC),

Universidade do Porto, Porto, §Centro de Investigacao das Tecnologias da Saude (CITS) – Instituto Politecnico da Saude Norte,

CESPU, Gandra-Paredes, –Servico de Dermatologia, Hospitais da Universidade de Coimbra, Coimbra, ††Instituto de

Farmacologia e Terapeutica Experimental, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, ‡‡Instituto de

Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Porto, and §§Centro de Investigacao em Ciencias da Saude

(CICS), Universidade da Beira Interior, Covilha, Portugal

*Correspondence: S Coimbra. E-mail: ssn.coimbra@gmail.com

AbstractBackground Psoriasis vulgaris is associated with overweight ⁄ obesity and with increased C-reactive protein (CRP),

tumour necrosis factor (TNF)-a, interleukin (IL)-6, leptin and resistin levels and decreased adiponectin levels.

Objectives To understand the role ⁄ relationship of adipokines, as well as CRP, in a Portuguese psoriatic population,

by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index

(PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy.

Methods A cross-sectional (n = 66) and longitudinal study (before and after 12 weeks of therapy; n = 44) was

performed; 10 patients started topical treatment, 17 narrow-band ultraviolet B (NBUVB) and 17 psolaren associated

with UVA (PUVA).

Results Patients presented significantly higher BMI, leptin, resistin, TNF-a, IL-6 and CRP and significantly lower

adiponectin values. CRP and IL-6 correlated with PASI. Adiponectin and leptin were more altered in patients with

higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After

treatment, a significant reduction in PASI, CRP, resistin, TNF-a and IL-6, and a significant rise in adiponectin were

observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical

therapy was not associated with any significant change, except for TNF-a. After NBUVB, a significant reduction was

observed in TNF-a and in CRP. For PUVA, we observed a significant reduction in TNF-a, IL-6 and CRP, and a

significant increase in adiponectin.

Conclusion In psoriatic patients, increased overweight ⁄ obesity was associated with raised leptin levels and decreased

adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight ⁄ obese psoriatic patients.

Resistin, IL-6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL-6,

appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem

to be more successful. Nonetheless, after NBUVB and PUVA, a low-grade inflammation still persists.

Received: 7 December 2009; Accepted: 5 February 2010

Keywordsadipokines, body mass index, C-reactive protein, psoriasis therapy, psoriasis vulgaris, severity

Conflict of interestThe authors have no financial or other relationships that could lead to conflict of interest; all authors state no conflict

of interest.

FundingThis study was supported by FCT (POCI ⁄ SAU – OBS ⁄ 58600 ⁄ 2004) and by FEDER and by CITS (01 ⁄ 09 ⁄ CITS ⁄ CESPU).

ª 2010 The Authors

JEADV 2010, 24, 1386–1394 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2010.03647.x JEADV

IntroductionPsoriasis vulgaris is associated with several risk factors for cardio-

vascular diseases (CVD) namely, increased oxidative stress,1–3 dis-

lipidaemia,1–8 inflammation,3,9–11 and more recently, with

overweight and obesity.3,12–16 Obesity is a pro-inflammatory state,

usually presenting a low-grade chronic inflammation, with

increased levels of tumour necrosis factor (TNF)-a, C-reactive

protein (CRP) and interleukin (IL)-6 that are positively related to

the body mass index (BMI).17,18

Body mass index may provide, however, a surrogate informa-

tion, as more important than the BMI value is the degree of

intra-abdominal fat visceral obesity.13,19 The adipose tissue has

been recognized as a metabolically active organ, secreting numer-

ous cytokines, referred as adipokines, that are important in the

inflammatory and atherosclerotic processes,20,21 namely, IL-6 and

TNF-a, that are significantly higher in plasma of obese patients.22

These two cytokines mediate the acute phase response.23 CRP, a

positive acute phase protein, is released in response to increased

levels of cytokines, such as IL-6 and TNF-a.

Adiponectin is known to inhibit the inflammatory response and

to protect against metabolic diseases and CVD.21,24 Adiponectin

seems to play an important role in atherogenesis,25 as high levels

are associated with high concentrations of high-density lipoprotein

cholesterol (HDLc), low triglyceride26,27 and oxidized low-density

lipoprotein levels28 and with low BMI values.3Moreover, adipo-

nectin reduces the production of TNF-a, IL-6, interferon-c, the

monocyte cell adhesion, the macrophage phagocytic activity and

increases insulin sensitivity and the repair of damaged vascula-

ture.13,29 Plasma concentrations of adiponectin are decreased in

obese subjects, particularly when obesity is mainly abdominal.

Overweight, obesity and, more recently, psoriasis have been associ-

ated with reduced adiponectin levels.3,30–33

Leptin and resistin may also play an important role in psoriasis

pathogenesis, at least in the obese patients. Serum leptin levels

seem to reflect the body fat mass. High levels of leptin seem to

enhance Th1 immune responses, and increase macrophage activ-

ity, with production of different cytokines, namely, TNF-a.31,34,35

Resistin is expressed by cells in the stromal compartment of the

adipose tissue, particularly, by the macrophages, and by peripheral

monocytes.34 It seems that there is a correlation, although weak,

between BMI and serum resistin levels.36 High resistin levels are

reported to be associated with the atherosclerotic process and, like

leptin, resistin has been shown to increase the expression of several

pro-inflammatory cytokines, including TNF-a and IL-6.37 Hyper-

leptinaemia and hyperresistinaemia have been already reported in

psoriatic patients.31,32,34,35,38,39

There are few studies evaluating simultaneously several circulat-

ing adipokine levels at the exacerbation phase of psoriasis vulgaris,

before starting a treatment and after the therapy. Indeed, some

studies evaluated only the levels of some adipokines at the active

stage of the disease31,32 and others studied only the changes in

those values after UVB therapy.34

We have previously shown3 that the risk changes in lipid profile

seem to be independent of the severity and duration of psoriasis,

although a trend towards lower values of HDLc was observed with

increasing Psoriasis Area and Severity Index (PASI) and that CRP

is enhanced in psoriasis and correlated with its severity. Cytokines,

such as adiponectin, leptin, resistin, IL-6 and TNF-a, apparently

crucial in obesity and inflammatory processes, may play an impor-

tant role in the pathogenesis of psoriasis. A study in psoriasis vul-

garis patients about the blood levels of those cytokines, recognized

as important in obesity and CVD and their relationship with the

severity of the disease, with obesity and with the type of therapy,

may contribute to highlight the role of those cytokines in the path-

ogenesis of psoriasis.

Our aim was to understand the role and the relationship of

adiponectin, leptin, resistin, IL-6, TNF-a and of CRP, in a Portu-

guese psoriatic population, by assessing the relationship of their

circulating levels with psoriasis severity, as defined by PASI and

with obesity, as defined by BMI. We also aimed to study the rela-

tionship of these cytokines with psoriasis therapy efficacy, by

studying psoriatic patients before and after treatment, searching

for a relationship with the commonly used therapies [topical ther-

apy, narrow-band ultraviolet B (NBUVB) and psolaren associated

with UVA (PUVA) therapy].

Materials and methods

Subjects and therapies

The protocol used was approved by the Committee on Ethics of

the University Hospital of Coimbra, and all the 66 psoriasis

vulgaris patients (31 women ⁄ 35 men) gave informed consent to

participate in the study. Psoriasis severity was evaluated by the

PASI Score.40 To diminish subjectivity, PASI was evaluated by the

same dermatologist. A PASI Score below 10 defined psoriasis as

mild, between 10 and 20 as moderate and above 20 as severe.41

Psoriasis was diagnosed between 2 months and 55 years before the

present study. All patients were clinically and analytically studied

in the active phase of the disease, before starting a therapy, and 44

patients were also evaluated after 12 weeks of treatment. Ten

patients (five women ⁄ five men) started topical treatment (calci-

potriol and betamethasone dipropionate, in combination or alter-

natively), 17 patients were treated with NBUVB (10 women ⁄ seven

men) and 17 patients received PUVA therapy (nine women ⁄ eight

men). The type of treatment was decided by the patients’ derma-

tologist, according to disease severity and the clinical and thera-

peutic history of the patients.

The NBUVB irradiation (311 ± 2 nm) was administered using

a Waldmann 7001 K cabin (UVA ⁄ UVB-TL01; Waldmann Medi-

zintechnik, Villigen-Schwenningen, Germany); the initial dose,

dependent on the phototype of the patient, was 0.1–0.3 J ⁄ cm2; an

increasing dose schedule based on an increase of 0.1 J ⁄ cm2 was

used in every session (thrice weekly) until a maximum dose of

2.5 J ⁄ cm2 was reached. UVA irradiation (320–400 nm) was

ª 2010 The Authors

Adipokine levels in Portuguese psoriatic patients 1387

administered using the same cabin; 2 h earlier, 8-methoxipsoralen

was administered (0.6 mg ⁄ kg body weight); the initial dose was 2–

3 J ⁄ cm2, according to the phototype; an increasing dose schedule

based on an increase of 0.5 J ⁄ cm2 was used in every session (thrice

weekly), until a maximum dose of 12 J ⁄ cm2 was reached. Eyes

and genital were shielded during the irradiation procedures.

The control group included 37 apparently healthy volunteers

(16 females ⁄ 21 males) with normal haematological and biochemi-

cal values that were matched with patients for age (Table 1) and

smoking habits.

Controls and patients presenting other skin diseases, diabetes

mellitus, inflammatory or infectious diseases, cardiovascular, liver

or kidney diseases, were excluded from the study. None of the

patients received any treatment for at least 1 month prior to inclu-

sion. Controls and patients were not under any dietary restriction

or therapy that could interfere with our results.

Assays

Blood sample was collected from non-fasting subjects in tubes

without and with anticoagulant (ethylenediaminetetraacetic acid)

and centrifuged to obtain serum and plasma respectively.

Plasma adiponectin and serum leptin, resistin, IL-6 and TNF-alevels were evaluated using enzyme-immunoassay (Human Adipo-

nectin; R&D Systems, Minneapolis, MN, USA; Leptin ELISA,

Mercodia, Uppsala, Sweden; Human Resistin ELISA, Human IL-6

ELISA and Human TNF-a ELISA; Bender MedSystems, Vienna,

Austria).

Serum CRP levels were evaluated by immunoturbidimetry [CRP

(latex) High-Sensitivity; Roche Diagnostics, Basel, Switzerland].

Statistical analysis

We used the Statistical Package for Social Sciences (SPSS, version 16

for Windows; SPSS, Chicago, IL, USA). To compare control with

patients before starting a therapy (T0), and after treatment (T12),

we used the Mann–Whitney test; to evaluate the differences

between T0 and T12, we used the Wilcoxon test. A P-value <0.05

was considered statistically significant. For analysis of confounding

factors, we used analysis of covariance (ANCOVA) after transforma-

tion of variables. The correlation analysis was performed by calcu-

lating the Spearman coefficient correlation.

ResultsWe observed that in the active stage of the disease (Table 1),

before starting a therapy, patients presented statistically signifi-

cantly higher leptin, resistin, TNF-a, IL-6 and CRP levels and sig-

nificantly lower adiponectin values. Patients, compared with

controls, presented a significantly higher BMI (Table 1). All the

statistical significances observed persisted after adjustment for

BMI (by performing analysis of covariance (ANCOVA), after trans-

formation of variables, using the SPSS).

As leptin values seemed to differ between genders,38 we evalu-

ated leptin for female and male patients and controls. Thus, we

found higher leptin values for female patients (P < 0.001). The

same difference was observed between women and men in control

(P = 0.001). Female patients presented significantly higher leptin

levels than female controls, which persisted after adjustment for

BMI, while male patients showed a trend towards higher values

compared with male controls (Table 1). No differences were

observed between genders for all the other parameters studied,

namely, for adiponectin.

We found that both CRP and IL-6 correlated significantly with

PASI (Fig. 1a–b) and that they correlated with each other

(r = 0.343; P = 0.005); CRP also correlated with resistin

(r = 0.301; P = 0.014). Confirming our previous data,3 adiponec-

tin correlated negatively with BMI (r = )0.379; P = 0.002). BMI

correlated with leptin (r = 0.314; P = 0.010) and this correlation

was also observed when considering female patients (r = 0.485;

P = 0.006), but not male patients.

To analyse our results in accordance with BMI, we divided the

patients into three groups: BMI lower than 25 (n = 19), BMI

Table 1 Characteristics of control and psoriatic patients

Control (n = 37) Psoriatic patients (n = 66) P-value

Leptin (ng ⁄ mL) 10.40 (5.45–16.05) 14.25 (7.58–29.60) 0.018

Men 6.55 (4.20–11.73) 9.30 (5.30–11.80) 0.147

Women 15.30 (8.60–25.30) 24.10 (18.10–43.40) 0.030

Resistin (pg ⁄ mL) 2150 (1688–3075) 3090 (2313–4808) 0.004

Adiponectin (ng ⁄ mL) 6122 (4116–7668) 4104 (3433–5948) <0.001

Tumour necrosis factor-a (pg ⁄ mL) 0.80 (0.40–1.65) 1.85 (0.70–4.80) <0.001

Interleukin-6 (pg ⁄ mL) 0.67 (0.35–1.00) 1.07 (0.66–2.22) <0.001

C-reactive protein (mg ⁄ L) 1.50 (0.60–2.58) 4.50 (1.54–8.91) <0.001

Age (years) 50.0 (35.0–58.0) 42.5 (32.8–57.0) 0.417

Duration of disease (years) – 18.0 (10.0–28.3) –

Body mass index (kg ⁄ m2) 24.06 (22.55–25.04) 27.49 (23.81–29.74) <0.001

Psoriasis Area and Severity Index – 18.8 (10.9–29.9) –

Cytokines and C- reactive protein values. Values expressed as median values (interquartile ranges).

ª 2010 The Authors

1388 Coimbra et al.

between 25 and 30 (n = 35) and BMI higher than 30 kg ⁄ m2

(n = 12). These three groups presented similar age, PASI and

duration of disease (data not shown). The group with BMI > 30

presented significantly higher leptin values than those presented

by BMI 25–30 and BMI < 25 groups, and higher than those pre-

sented by the control group (Fig. 2a); however, 58% (n = 7) of

the BMI > 30 patients were women. In women (Fig. 2a1), the

BMI < 25 group presented lower values than those of the other

two groups, and these two differed significantly from control

female group. Considering men (Fig. 2a2), BMI > 30 group pre-

sented significantly higher leptin values than those presented by

the group BMI 25–30 and by the control group men. Considering

adiponectin (Fig. 2b), the BMI > 30 group presented significantly

lower values than those presented by the BMI < 25 group, and

lower than those presented by the control group; the adiponectin

in the group 25–30 BMI also presented a significantly lower value

than the control, and a trend towards lower adiponectin levels

than the BMI < 25 group (Fig. 2b). We did not find any statisti-

cally significant difference in the other studied parameters among

the three groups.

According to PASI, 17% of the patients (n = 11) presented mild

psoriasis, 36% (n = 24) presented moderate psoriasis and 47%

(n = 31) presented severe psoriasis. These three groups presented

similar age, BMI and duration of disease (data not shown). Con-

cerning adiponectin, we confirmed our previous results,3 a trend

towards lower values of adiponectin was observed in moderate and

severe forms of psoriasis (Fig. 3a); these forms also presented

significantly lower values as compared with the control group.

Concerning resistin (Fig. 3b), the severe forms presented signifi-

cantly higher values when compared with moderate forms and

with control. The degree of inflammation, suggested by IL-6 and

CRP, showed that IL-6 (Fig. 3c) was significantly higher in the

severe form compared with the mild one and moderate and severe

forms presented higher values than the control group; CRP

(Fig. 3d) was significantly higher in the severe form, when com-

pared with moderate forms of psoriasis, and higher, although not

significant, with the mild form; all psoriasis forms differed signifi-

cantly from control. We did not find any statistically significant

difference in the other studied parameters among the three groups.

The weight of the patients did not change during and after

treatment, as they did not alter their nutritional habits, did not

receive any medication that could interfere with their weight and

did not perform a different physical exercise activity during the

treatment. As expected, a significant decrease in psoriasis severity,

as defined by PASI, was recorded after treatment (Table 2). At

T12 (Table 2), a significant reduction in resistin, TNF-a and IL-6,

and a significant rise in adiponectin were observed. Nonetheless,

adiponectin values remained lower than those of the control. Con-

sidering CRP, a significant reduction was found; yet, CRP values

remained higher from those observed in controls. IL-6 levels

remained higher than those of controls, but significance was lost

after BMI adjustment.

Analysing the results according to the used therapies (Table 3),

we found that topical therapy was not associated with any signifi-

cant change, except for TNF-a that was significantly reduced; at T0

and at T12, TNF-a values were higher than those of the control.

(a) (b)60.00

r = 0.301P = 0.014

r = 0.283P = 0.021

0.0 10.0 20.0 30.0 40.0PASI

50.0 60.0 70.0 0.0 10.0 20.0 30.0 40.0PASI

50.0 60.0 70.0

Figure 1 Correlations observed for patients between: (a) C-reactive protein (CRP) and Psoriasis Area and Severity Index (PASI);

(b) interleukin-6 and PASI.

ª 2010 The Authors

After NBUVB treatment (Table 3), a significant reduction was

observed in TNF-a and in CRP values. The resitin and CRP levels,

at T0, were significantly higher than those of the control and CRP

remained significantly higher.

For PUVA therapy (Table 3), we observed a significant reduc-

tion in TNF-a, IL-6 and CRP, and a significant increase in adipo-

nectin values. The adiponectin, TNF-a, IL-6 and CRP were

significantly different from control at T0 and they maintained

these differences at T12 (except for TNF-a).

DiscussionIn the present study, we demonstrated that Portuguese psoriatic

patients showed an incidence of overweight ⁄ obesity as 71% of

them presented a BMI ‡ 25 kg ⁄ m2, which is in accordance with

previous results42 that found for Caucasians a positive association

between obesity and psoriasis. We also observed, compared with

controls, higher leptin, resistin, TNF-a and IL-6 levels, and lower

adiponectin levels. As visceral adipose tissue is the major source of

adiponectin and leptin, it is possible to conclude that also a high

10 000

Control Less 25 25–30BMI (kg/m2)

Above 30

Control < 25 25–30

BMI (kg/m2)> 30

Control < 25 25–30

BMI (kg/m2)> 30

Control Less 25 25–30BMI (kg/m2)

Above 30

P < 0.001

P = 0.018P = 0.052

P = 0.001P = 0.001

P = 0.003P = 0.015

Females

P = 0.003

P = 0.025

P = 0.006 P = 0.017

P = 0.002

(a) (a1)

Figure 2 Values for control and for patients, according to body mass index, of: (a) leptin; (b) adiponectin.

ª 2010 The Authors

1390 Coimbra et al.

incidence of adiposity is observed in the Portuguese psoriatic

patients studied. Obesity is referred as having an adverse effect on

psoriasis,43 which, thus, could be a consequence of the enhance-

ment in the production of resistin, leptin, IL-6 and TNF-a, and of

the decreased synthesis of adiponectin.

Visceral adipose tissue increases the secretion of cytokines, such

as IL-6 and TNF-a, known to mediate the acute phase response.23

CRP is released in response to increased levels of circulating cyto-

kines, namely, IL-6 and TNF-a. Psoriasis, as an inflammatory con-

dition, is also associated with increased levels of CRP, IL-6 and

TNF-a.11,23 Our results are consistent with this, showing raised

levels of CRP, IL-6 and TNF-a. Furthermore, we found a positive

correlation of IL-6 and of CRP values with psoriasis severity, as

defined by PASI, suggesting that they may be useful as markers of

psoriasis severity.

Considering leptin, we found, as expected, and in accordance

with Chen et al. study,38 higher levels in female psoriatic patients.

Leptin serum levels seemed to reflect the body fat mass and consis-

tent with this, we detected for female patients that increased levels

of leptin were correlated with higher BMI. Moreover, the

BMI < 25 female group presented significantly lower values of lep-

tin compared with other two groups with higher BMI (Fig. 2a1);

in men, the BMI > 30 group presented higher values than the

BMI 25–30 and the control group (Fig. 2a2). Thus, hyperleptina-

emia in psoriatic patients seems to be related to patient over-

weight ⁄ obesity. As leptin can promote Th1 immune response and

10 000

6.00 30.00

Control Under 10

P = 0.339P = 0.002

P = 0.001

P = 0.044

P = 0.076

P = 0.008

P = 0.016P = 0.010 P < 0.001

P = 0.011P < 0.001

P = 0.028P = 0.002

P = 0.019

10–20PASI

Above 20

Control Under 10 10–20PASI

Above 20 Control Under 10 10–20PASI

Above 20

Control Under 10 10–20PASI

Above 20

(a) (b)

(c) (d)

Figure 3 Values for control and for patients, according to Psoriasis Area and Severity Index (PASI), of: (a) adiponectin; (b) resistin;(c) interleukin-6; (d) C-reactive protein.

ª 2010 The Authors

suppress type 2 cytokine production,34 leptin may play an impor-

tant role in psoriasis pathogenesis, at least in women and in over-

weight ⁄ obese psoriatic patients. In relation to adiponectin, lower

values were observed in psoriasis. Pro-inflammatory factors, such

as IL-6 and TNF-a, are known to suppress adiponectin production

by adipose tissue,29 thus the elevation observed in IL-6 and TNF-ain psoriatic patients might cause a decrease in the production of

adiponectin, explaining the lower levels detected. Furthermore,

adiponectin correlated inversely with BMI, and adiponectin values

were lower in the patients with higher BMI (Fig. 2b). Therefore, in

the present study, increasing BMI in psoriatic patients is associated

with higher leptin and lower adiponectin levels.

Increasing psoriasis severity (Fig. 3) was associated with a signif-

icantly higher inflammatory degree, as suggested by CRP and IL-6

values. In our study, we found higher CRP and IL-6 values in the

more severe forms of psoriasis vulgaris (Fig. 3c–d) and, moreover,

a significantly positive correlation between CRP and PASI and IL-

6 and PASI (Fig. 1a–b). CRP in combination with IL-6 values may

therefore be useful in monitoring the evolution of the disease and

the therapeutic response.

Moderate and severe forms of psoriasis presented a trend

towards lower values of adiponectin (Fig. 3a). The lower adipo-

nectin levels found for psoriatic patients seem to be dependent on

the overweight ⁄ obesity of the patient and also appear to be related

to the severity of psoriasis.

Consistent with the study of Johnston et al.34 that found a cor-

relation between resistin and psoriasis severity, we found that resi-

stin levels were higher in the more severe forms (Fig. 3c); thus

resistin levels appear to be associated with the severity of psoriasis.

Resistin, known to induce the production of pro-inflammatory

cytokines, such as IL-6 and TNF-a, that in turn can stimulate

more resistin synthesis,34 presented higher levels in psoriatic

patients, which may suggest a pathogenic role for resistin in psori-

asis, especially related to psoriasis severity.

The analytical changes observed after treatment, linked to a sig-

nificant reduction in PASI, seem to reflect the inhibition of cellular

proliferation and of release of cell activation products, including

pro-inflammatory mediators. In accordance, resistin, adiponectin,

TNF-a, IL-6 and CRP presented a significant improvement after

treatment. However, and independent of the therapy used, it

seems that a low-grade of inflammation persists.

We found no significant change in the analytical parameters

studied with topical therapy, except for TNF-a that was significantly

reduced, confirming that the reduction in the hyperproliferative

process within the lesions is important for inflammatory response.

Actually, this is a common finding in the course of the three thera-

pies. We must refer that, at T0, these patients showed milder psoria-

sis, as defined by PASI, and did not present significant differences

from the control group, except for TNF-a, which, although reduced

after treatment, was still significantly higher than in controls, further

strengthening the role of inflammation in psoriasis.

Patients treated with NBUVB, presenting a PASI higher than

the latter group, showed resistin and CRP values higher than con-

trols. After NBUVB treatment, CRP was still higher than in the

control group; a significant TNF-a and CRP reduction was

observed. The differences observed at T0 seem to be mostly related

to the more severe disease presentation. The therapy was successful

as defined by PASI; however, CRP still presented higher values

than controls, reflecting a persistently increased inflammatory risk.

In PUVA group (T0), with the highest PASI, higher values than

controls were observed for TNF-a, IL-6 and CRP, and lower values

for adiponectin. The reduction in inflammation seems to be more

effective with PUVA, as TNF-a, IL-6, CRP and adiponectin pre-

sented a significant improvement, although sustaining values that

are still different from those of the control (except for TNF-a).

In summary, in psoriatic patients, increased overweight ⁄ obesity

is associated with raised levels of leptin and decreased levels of

adiponectin. Leptin, by promoting activation of T cells, induces

Table 2 Cytokines and C-reactive protein (CRP) values in psoriatic patients, before starting (T0) and after 12th weeks of treatment

(T12), and in a control group

Control (C) (n = 37) Psoriatic patients (n = 44)

Starting (T0) 12th week (T12) P-value (T0 vs. T12)

Leptin (ng ⁄ mL) 10.40 (5.45–16.05) 17.90‡‡ (9.35–30.60) 16.15†† (8.00–29.75) 0.058

Men 6.55 (4.20–11.72) 10.00 (6.60–11.80) 8.10 (6.30–11.20) 0.214

Women 15.30 (8.60–25.30) 24.00 (17.90–46.85) 21.50 (16.50–48.55) 0.216

Resistin (pg ⁄ mL) 2150 (1688–3075) 2991‡ (2090–4690) 2688 (1896–4039) 0.039

Adiponectin (ng ⁄ mL) 6122 (4116–7668) 4097‡‡‡ (3387–6083) 4805†† (3156–6408) 0.011

TNF-a (pg ⁄ mL) 0.80 (0.40–1.65) 1.55‡‡ (0.70–3.35) 1.15 (0.53–1.95) <0.001

IL-6 (pg ⁄ mL) 0.67 (0.35–1.00) 1.09‡‡‡ (0.61–2.14) 1.03*,† (0.37–1.74) 0.010

CRP (mg ⁄ L) 1.50 (0.60–2.58) 3.11‡‡‡ (1.26–6.75) 2.46†† (1.12–5.60) 0.012

PASI – 15.8 (10.4–26.9) 2.9 (1.5–5.1) <0.001

Psoriasis severity was evaluated by Psoriasis Area and Severity Index (PASI). Values expressed as median (interquartile ranges).

TNF-a, tumour necrosis factor-a; IL-6, interleukin-6.

*Loss of significance when adjusted for BMI.‡P(C vs. T0) < 0.05; ‡‡P(C vs. T0) £ 0.01; ‡‡‡P(C vs. T0) £ 0.001; †P(C vs. T12) < 0.05; ††P(C vs. T12) £ 0.01; †††P(C vs. T12) £ 0.001.

ª 2010 The Authors

1392 Coimbra et al.

production of IL-6 and TNF-a and may contribute to enhance the

inflammatory process in overweight ⁄ obese psoriatic patients. Resi-

stin, IL-6, CRP and also adiponectin levels appear to be dependent

on psoriasis severity. CRP, together with IL-6 values, appears to be

a useful marker of psoriasis severity, allowing the monitorization

of the evolution of the disease and of the therapeutic response.

Both NBUVB and PUVA were effective; however, the reduction in

inflammation seems to be more successful with PUVA. Nonethe-

less, after NBUVB and PUVA effective treatments, a low-grade

inflammatory process still persists.

AcknowledgementsThis study was supported by FCT (POCI ⁄ SAU–OBS ⁄ 58600 ⁄2004) and by FEDER, and by CITS (01 ⁄ 09 ⁄ CITS ⁄ CESPU).

We thank the Departamento de Analises Clınicas of Instituto

Politecnico da Saude Norte. But, they had no role in the

design and conduct of the study, in the collection, analysis and

interpretation of data or in the preparation, review or approval

of the manuscript. We are indebted to FCT (POCI ⁄ SAU – OBS ⁄58600 ⁄ 2004), to FEDER and to CITS (01 ⁄ 09 ⁄ CITS ⁄ CESPU).

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ª 2010 The Authors

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Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass...

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