EXTENDED REPORT

Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus

L C W Lit¹, C K Wong¹, L S Tam², E K M Li², C W K Lam¹

¹ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
² Department of Medicine and Therapeutics, The Chinese University of Hong Kong

Correspondence to:
Professor Christopher Wai-Kei Lam
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; waikeilam{at}cuhk.edu.hk

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 GRO, and proinflammatory cytokines IL18, IFN, 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, GRO, 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, GRO, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFN, 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.

Abbreviations: CBA, cytometric bead array; GRO, growth regulated oncogenes ; IFN, interferon ; IL, interleukin; IP10, chemokine interferon inducible protein 10; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein-1; MIG, monokine induced by IFN; PBMC, peripheral blood mononuclear cells; PHA, mitogen phytohaemagglutinin; RANTES, regulated upon activation normal T cell expressed and secreted; RSLE, systemic lupus erythematosus with renal disease; SLE, systemic lupus erythematosus; SLEDAI,; systemic lupus erythematosus disease activity index,; TARC, thymus and activation regulated chemokine; Th, T helper; TNF, tumour necrosis factor

Keywords: systemic lupus erythematosus; SLEDAI; inflammatory chemokines; IL18

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