Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement.
Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-gamma (IFN-gamma ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-beta1, Tumour necrosis factor (TNF)-alpha, sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1alpha and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNFalpha and MCP-1 but reduced amounts of gamma-IFN and MDC. IL6, IL10, IL18, MIP-1alpha and TNFalpha measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-beta1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.
Scala
E
E
Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico [IDI--IRCCS], Rome, Italy. e.scala@idi.it
Pallotta
S
S
Frezzolini
A
A
Abeni
D
D
Barbieri
C
C
Sampogna
F
F
De Pità
O
O
Puddu
P
P
Paganelli
R
R
Russo
G
G
D002460:Cell Line; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis*; D015154:Esophageal Motility Disorders / Q000150:complications / Q000276:immunology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000150:complications / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10