Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus.
BACKGROUND
Chemokines are involved in leucocyte chemotaxis. Infiltrating leucocytes play an important role of tissue injury in systemic lupus erythematosus (SLE).


OBJECTIVE
To investigate the role of inflammatory chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis and disease activity.


METHODS
Plasma concentrations and ex vivo peripheral blood mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1, TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4, and IL10 were assayed in 80 SLE patients with or without renal disease and 40 healthy controls by immunofluorescence flow cytometry and enzyme linked immunosorbent assay.


RESULTS
Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18 concentrations in all SLE patients were higher than in controls, and correlated significantly with SLEDAI score (all p<0.05). In SLE patients without renal disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18 correlated with disease activity (all p<0.05). Plasma IL18 concentration correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their difference in disease activity (all p<0.05). Patients with renal disease had an augmented ex vivo release of RANTES.


CONCLUSIONS
The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
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D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002478:Cells, Cultured; D054414:Chemokine CCL17; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D018946:Chemokine CCL5 / Q000032:analysis / Q000097:blood; D054370:Chemokine CXCL9; D018925:Chemokines / Q000032:analysis / Q000097:blood*; D019742:Chemokines, CC / Q000032:analysis / Q000097:blood; D019743:Chemokines, CXC / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D020382:Interleukin-18 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
C106230:CCL17 protein, human; C111835:CCL2 protein, human; C080810:CXCL9 protein, human; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054370:Chemokine CXCL9; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D007371:Interferon-gamma