ABSTRACT
Body
fat has regulatory functions through producing cytokines and adipokines
whose role in the pathogenesis of Systemic Sclerosis (SSc) is currently
emerging. Changes in body mass, either overweight or underweight status,
entail a dysregulation of the cytokines/adipokines network that may
impact on SSc disease activity. We evaluated serum levels of adipokines
and cytokines in SSc patients and correlated them to clinical features
and body mass index (BMI) categories.
The study included 89 SSc patients and 26 healthy donors (HD). Serum
levels of adiponectin, leptin, resistin, visfatin, TNFα, IFNγ, IL-2,
IL-10, and IL-17A were measured by Multiplex Immunoassay, and correlated
to BMI, waist to hip ratio, and disease specific features. Mann-Whitney
U-test or t-Student for unpaired data, Kruskal-Wallis test or ANOVA,
were used for comparisons between groups. Spearman’s or Pearson’s test
were used for correlation analysis.
Serum levels of TNFα, IL-2, leptin, and resistin, were significantly
higher in SSc than in HD. The highest levels of IL-17A, IL-2, IL-10,
leptin and visfatin were detected in obese SSc patients (p
<0.01 ). Conversely, underweight SSc patients showed the
highest
TNFα
levels
(p<0.05 ),
which were negatively correlated with BMI (p=0.05 ). No
correlation between adipokines/cytokines and clinical characteristics
was found.
Adipokines, IL-2, IL-10 and IL-17A were found to be increased in obese
SSc patients, but whether they play a role in the pathogenesis of the
disease remains to be investigated. Intriguingly, underweight patients
had higher TNFα levels, suggesting a potential role of TNFα in inducing
the cachexia observed in long-lasting disease.
Systemic sclerosis (SSc) is a connective tissue disease characterized by
small vessels vasculopathy associated with fibrosis of multiple organs.
The pathogenesis is unclear, but an autoimmune dysregulation and an
abnormal inflammatory response seem to be involved in the early stage of
the disease. Emerging evidence suggests that white adipose tissue (WAT),
besides having the role of energy storage, is now acknowledged as a
pleiotropic organ with endocrine functions and regulating immune and
inflammatory responses, being a source of cytokines and adipokines
(leptin, adiponectin, visfatin, resistin) (1). Indeed, obesity may have
an impact on disease activity as well as on clinical response of
patients with rheumatoid arthritis and psoriatic arthritis (2,3). In
obese subjects, leptin induces the expression of adhesion molecules on
endothelial cells and activates macrophages, while hindering adiponectin
production by adipocytes, contributing to the “low-grade inflammatory
state” associated with obesity (1).
Recently, the role of cytokines/adipokines in the pathophysiology of SSc
has become a matter of investigation but studies correlating them with
the clinical subsets or particular organ involvement were not always
consistent. Serum leptin levels were found to be positively correlated
with body mass index (BMI), negatively with disease activity in SSc
patients, but not increased in comparison with healthy controls (4,5).
Conversely, serum levels of leptin, resistin and TNFα were higher in a
small cohort of 16 SSc patients than in control subjects but no
correlation with skin involvement, disease duration and disease activity
was seen (6). A newly discovered adipokine, adipsin, was significantly
higher in limited cutaneous SSc (lcSSc) than in diffuse cutaneous SSc
(dcSSc) and was strongly associated with pulmonary arterial hypertension
(7). Interestingly, adiponectin seems to play a protective role in SSc,
as the levels were found to be low in dcSSc patients and inversely
correlated with the extension of skin fibrosis, C-reactive protein (CRP)
and erythrocyte sedimentation rate (ESR) (5,8-10). However, the
interweave among body mass, cytokines/adipokines and SSc clinical
phenotypes has been poorly investigated.
In this study, we aimed at evaluating serum levels of adipokines
(leptin, resistin, visfatin, adiponectin) and cytokines (TNFα,
Interferon-gamma (IFNγ), IL-2, IL-10, IL-17A) in SSc patients according
to BMI categories and disease specific characteristics.