- Oral presentation
Adipocytokines and autoimmunity
Arthritis Research & Therapy volume 13, Article number: O8 (2011)
By definition, adipo(cyto)kines are cytokine-like mediators produced mainly by adipose tissue. In the human body, they participate in regulating a variety of physiological functions related to energy metabolism  and inflammation . Increased or decreased adipokine levels are associated with autoimmune diseases including diabetes mellitus type 1 (DMT1) , rheumatoid arthritis (RA) [4, 5], ankylosing spondylitis (AS) , systemic sclerosis (SSc) , systemic lupus erythematosus (SLE)  and Behçet's disease [9–12].
In vitro data suggest that adipokines may contribute to the progression of RA as they are potent inducers of proinflammatory cytokines, chemokines and matrix metalloproteinases (MMP) in RA effector cells [13–16].
SSc also appears to be associated with adipokines. Contrary to RA, in which substantial intraarticular degradation of extracellular matrix occurs, SSc is characterized by excessive fibrosis. In vitro data and data from animal models of fibrosis point towards a dual role of the adipokine adiponectin as presented by numerous groups at the EULAR congress in London, specifically an antifibrotic effect in later stages of SSc and a profibrotic effect in earlier stages, which appears to be induced by proinflammatory cytokines. Likewise, leptin is involved in the development of liver fibrosis [17–19].
So far, no or only little functional information is available regarding the role of adipokines in other autoimmune diseases. Serum level and clinical correlation analyses, however, suggest an association with adipokines.
In AS, elevated resistin serum levels have been found, while adiponectin levels remained unchanged [6, 20]. On the other hand, leptin is discussed controversially in AS. Serum levels were decreased in AS according to two studies [20, 21], while they were increased according to another . Also, while correlations of leptin with parameters of inflammation (C-reactive protein, IL-6) and disease activity (Bath Ankylosing Spondylitis Disease Activity Index) have been found by Park et al. , no such correlations could be found by Toussirout et al. . Interestingly, peripheral blood mononuclear cells (PBMC) from AS patients express and secrete more leptin, IL-6 and TNF-α than PBMC from control subjects. Additionally, stimulation of PBMC from AS patients with exogenous leptin led to a significantly increased IL-6 and TNF-α production . Hence, leptin might be involved in the pathogenesis of AS.
In SLE, resistin, for example, has been shown to be associated with general inflammation and bone loss, suggesting a proinflammatory and disease-promoting function .
However, the exact role of adipokines especially in SSc, AS and SLE is still unclear and will require further investigation. Also, further research is warranted to show whether adipokines may represent potential therapeutic targets in this diseases.
Rajala MW, Scherer PE: Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003, 144: 3765-3773. 10.1210/en.2003-0580.
Neumann E, Frommer KW, Vasile M, Muller-Ladner U: Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases?. Arthritis Rheum. 2011, 63: 1159-1169. 10.1002/art.30291.
Galler A, Gelbrich G, Kratzsch J, Noack N, Kapellen T, Kiess W: Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study. Eur J Endocrinol. 2007, 157: 481-489. 10.1530/EJE-07-0250.
Schäffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Schölmerich J, Müller-Ladner U, Gay S: Adipocytokines in synovial fluid. JAMA. 2003, 290: 1709-1710. 10.1001/jama.290.13.1709-c.
Laurberg TB, Frystyk J, Ellingsen T, Hansen IT, Jorgensen A, Tarp U, Hetland ML, Horslev-Petersen K, Hornung N, Poulsen JH: Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid- and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls. J Rheumatol. 2009, 36: 1885-1891. 10.3899/jrheum.080907.
Kocabas H, Kocabas V, Buyukbas S, Melikoglu MA, Sezer I, Butun B: The serum levels of resistin in ankylosing spondylitis patients: a pilot study. Rheumatol Int. 2010, [Epub]
Kotulska A, Kucharz EJ, Brzezinska-Wcislo L, Wadas U: A decreased serum leptin level in patients with systemic sclerosis. Clin Rheumatol. 2001, 20: 300-302. 10.1007/s100670170053.
Harle P, Pongratz G, Weidler C, Buttner R, Scholmerich J, Straub RH: Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis. 2004, 63: 809-816. 10.1136/ard.2003.011619.
Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A: Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch Med Res. 2010, 41: 457-463. 10.1016/j.arcmed.2010.08.012.
Sezen H, Okumus S, Pehlivan Y, Dilli I, Tarakcioglu M, Onat AM: Visfatin Levels in Behcet's Disease. Inflammation. 2011, [Epub]
Yalcindag FN, Yalcindag A, Batioglu F, Caglayan O, Kisa U, Ozdemir O: Evaluation of serum resistin levels in patients with ocular and non-ocular Behcet's disease. Can J Ophthalmol. 2008, 43: 473-475. 10.3129/I08-081.
Evereklioglu C, Inaloz HS, Kirtak N, Doganay S, Bulbul M, Ozerol E, Er H, Ozbek E: Serum leptin concentration is increased in patients with Behcet's syndrome and is correlated with disease activity. Br J Dermatol. 2002, 147: 331-336. 10.1046/j.1365-2133.2002.04703.x.
Ehling A, Schaffler A, Herfarth H, Tarner IH, Anders S, Distler O, Paul G, Distler J, Gay S, Scholmerich J: The potential of adiponectin in driving arthritis. J Immunol. 2006, 176: 4468-4478.
Frommer KW, Zimmermann B, Meier FM, Schroder D, Heil M, Schäffler A, Büchler C, Steinmeyer J, Brentano F, Gay S: Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis Rheum. 2010, 62: 2886-2899. 10.1002/art.27616.
Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A: Resistin, an adipokine with potent proinflammatory properties. J Immunol. 2005, 174: 5789-5795.
Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, Kyburz D: Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum. 2007, 56: 2829-2839. 10.1002/art.22833.
Ikejima K, Takei Y, Honda H, Hirose M, Yoshikawa M, Zhang YJ, Lang T, Fukuda T, Yamashina S, Kitamura T, Sato N: Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology. 2002, 122: 1399-1410. 10.1053/gast.2002.32995.
Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA: Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002, 35: 762-771. 10.1053/jhep.2002.32029.
Wang J, Leclercq I, Brymora JM, Xu N, Ramezani-Moghadam M, London RM, Brigstock D, George J: Kupffer cells mediate leptin-induced liver fibrosis. Gastroenterology. 2009, 137: 713-723. 10.1053/j.gastro.2009.04.011.
Toussirot E, Streit G, Nguyen NU, Dumoulin G, Le Huede G, Saas P, Wendling D: Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis. Metabolism. 2007, 56: 1383-1389. 10.1016/j.metabol.2007.05.009.
Sari I, Demir T, Kozaci LD, Akar S, Kavak T, Birlik M, Onen F, Akkoc N: Body composition, insulin, and leptin levels in patients with ankylosing spondylitis. Clin Rheumatol. 2007, 26: 1427-1432. 10.1007/s10067-006-0509-6.
Park MC, Lee SW, Choi ST, Park YB, Lee SK: Serum leptin levels correlate with interleukin-6 levels and disease activity in patients with ankylosing spondylitis. Scand J Rheumatol. 2007, 36: 101-106. 10.1080/03009740600991760.
Park MC, Chung SJ, Park YB, Lee SK: Pro-inflammatory effect of leptin on peripheral blood mononuclear cells of patients with ankylosing spondylitis. Joint Bone Spine. 2009, 76: 170-175. 10.1016/j.jbspin.2008.04.018.
Almehed K, d'Elia HF, Bokarewa M, Carlsten H: Role of resistin as a marker of inflammation in systemic lupus erythematosus. Arthritis Res Ther. 2008, 10: R15-10.1186/ar2366.
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Frommer, K.W., Neumann, E. & Müller-Ladner, U. Adipocytokines and autoimmunity. Arthritis Res Ther 13, O8 (2011). https://doi.org/10.1186/ar3412
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
- Peripheral Blood Mononuclear Cell
- Ankylose Spondylitis
- Adiponectin Level