Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

被引:95
作者
Tsilioni, Irene [1 ]
Russell, Irwin J. [5 ]
Stewart, Julia M. [1 ]
Gleason, Rae M. [6 ]
Theoharides, Theoharis C. [1 ,2 ,3 ,4 ]
机构
[1] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Immunopharmacol & Drug Discovery Lab, Boston, MA 02111 USA
[2] Tufts Univ, Dept Psychiat, Dept Internal Med, Boston, MA 02111 USA
[3] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA
[4] Tufts Med Ctr, Boston, MA USA
[5] Fibromyalgia Res & Consulting, Arthrit & Osteoporosis Ctr South Texas, San Antonio, TX USA
[6] Natl Fibromyalgia & Chron Pain Assoc, Logan, UT USA
基金
美国国家卫生研究院;
关键词
CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; SUBSTANCE-P; VASCULAR-PERMEABILITY; DURA-MATER; HUMAN SKIN; ALPHA; RECEPTOR; EXPRESSION; SECRETION;
D O I
10.1124/jpet.115.230060
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain affecting more women than men. Even though clinical studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or reliable objective markers has hampered development of effective treatments. Here we report that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP), and SP-structurally-related hemokinin-1 (HK-1) were significantly (P = 0.026, P < 0.0001, and P = 0.002, respectively) elevated (0.82 +/- 0.57 ng/ml, 0.39 +/- 0.18 ng/ml, and 7.98 +/- 3.12 ng/ml, respectively) in the serum of patients with FMS compared with healthy controls (0.49 +/- 0.26 ng/ml, 0.12 +/- 0.1 ng/ml, and 5.71 +/- 1.08 ng/ml, respectively). Moreover, SP and HK-1 levels were positively correlated (Pearson r = 0.45, P = 0.002) in FMS. The serum concentrations of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF) were also significantly (P = 0.029 and P = 0.006, respectively) higher (2.97 +/- 2.35 pg/ml and 0.92 +/- 0.31 pg/ml, respectively) in the FMS group compared with healthy subjects (1.79 +/- 0.62 pg/ml and 0.69 +/- 0.16 pg/ml, respectively). In contrast, serum IL-31 and IL-33 levels were significantly lower (P = 0.0001 and P = 0.044, respectively) in the FMS patients (849.5 +/- 1005 pg/ml and 923.2 +/- 1284 pg/ml, respectively) in comparison with healthy controls (1281 +/- 806.4 pg/ml and 3149 +/- 4073 pg/ml, respectively). FMS serum levels of neurotensin were not different from controls. We had previously shown that CRH and SP stimulate IL-6 and TNF release from mast cells (MCs). Our current results indicate that neuropeptides could stimulate MCs to secrete inflammatory cytokines that contribute importantly to the symptoms of FMS. Treatment directed at preventing the secretion or antagonizing these elevated neuroimmune markers, both centrally and peripherally, may prove to be useful in the management of FMS.
引用
收藏
页码:664 / 672
页数:9
相关论文
共 122 条
[1]   Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the 'single syndrome' hypothesis [J].
Abbi, B. ;
Natelson, B. H. .
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, 2013, 106 (01) :3-9
[2]  
[Anonymous], TRENDS IMMUNOL, V27, P32
[3]  
ANSEL JC, 1993, J IMMUNOL, V150, P4478
[4]   The Pathophysiology, Diagnosis and Treatment of Fibromyalgia [J].
Arnold, Lesley M. .
PSYCHIATRIC CLINICS OF NORTH AMERICA, 2010, 33 (02) :375-+
[5]   Substance P (SP) Induces Expression of Functional Corticotropin-Releasing Hormone Receptor-1 (CRHR-1) in Human Mast Cells [J].
Asadi, Shahrzad ;
Alysandratos, Konstantinos-Dionysios ;
Angelidou, Asimenia ;
Miniati, Alexandra ;
Sismanopoulos, Nikolaos ;
Vasiadi, Magdalini ;
Zhang, Bodi ;
Kalogeromitros, Dimitrios ;
Theoharides, Theoharis C. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2012, 132 (02) :324-329
[6]   VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3 [J].
Baroni, Enrico ;
Biffi, Mauro ;
Benigni, Fabio ;
Monno, Antonia ;
Carlucci, Donatella ;
Carmeliet, Geert ;
Bouillon, Roger ;
D'Ambrosio, Daniele .
JOURNAL OF LEUKOCYTE BIOLOGY, 2007, 81 (01) :250-262
[7]  
Bazzichi L, 2007, CLIN EXP RHEUMATOL, V25, P225
[8]   Unique immunologic patterns in fibromyalgia [J].
Behm, Frederick G. ;
Gavin, Igor M. ;
Karpenko, Oleksiy ;
Lindgren, Valerie ;
Gaitonde, Sujata ;
Gashkoff, Peter A. ;
Gillis, Bruce S. .
BMC CLINICAL PATHOLOGY, 2012, 12
[9]   Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients [J].
Blanco, Ignacio ;
Beritze, Nana ;
Argueelles, Mario ;
Carcaba, Victoriano ;
Fernandez, Fernando ;
Janciauskiene, Sabina ;
Oikonomopoulou, Katerina ;
de Serres, Frederick J. ;
Fernandez-Bustillo, Enrique ;
Hollenberg, Morley D. .
CLINICAL RHEUMATOLOGY, 2010, 29 (12) :1403-1412
[10]   Inflammatory/Stress Feedback Dysregulation in Women with Fibromyalgia [J].
Bote, Maria E. ;
Garcia, Juan J. ;
Hinchado, Maria D. ;
Ortega, Eduardo .
NEUROIMMUNOMODULATION, 2012, 19 (06) :343-351