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Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Feb 2003; 62(2): 113–119.
PMCID: PMC1754424

Interleukin 7 stimulates tumour necrosis factor α and Th1 cytokine production in joints of patients with rheumatoid arthritis


Background: A large number of activated T cells are found in the joints of patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a T cell growth factor and a regulator of Th1 and Th2 cytokine production, is produced by synoviocytes from patients with RA.

Objective: To investigate the effect on proinflammatory cytokine production of synovial fluid mononuclear cells (SFMC) and the mechanism by which IL7 influences CD4+ T cell activity in patients with RA.

Methods: In a cross sectional group of patients with RA, IL7 levels were compared with those of healthy controls and related to disease activity. The effect of IL7 on cytokine production was tested by RA SFMC and on SF CD4+ T cells in the presence of mononuclear cells (MC). Production of tumour necrosis factor α (TNFα), IL1ß, interferon γ (IFNγ), and IL4 was measured by enzyme linked immunosorbent assay (ELISA) and by single cell FACS analysis. Expression of the IL7 receptor α chain on CD4+ T cells (essential for IL7 signalling) was assessed. Direct effects of IL7 on isolated synovial fluid (SF) CD4+ T cells were studied by cytokine analysis. By neutralisation of IL12 in MC cultures, indirect effects of IL7 on T cells through accessory cells were studied.

Results: IL7 serum levels were higher in patients with RA than in healthy controls and correlated positively with C reactive protein levels. IL7 stimulated TNFα production by SFMC and very potently stimulated IFNγ and TNFα production by SF CD4+ T cells. These effects were probably mediated through the IL7 receptor α chain, which was abundantly expressed on SF CD4+ T cells. Besides the direct stimulation of T cell cytokine production by IL7, its action was partly dependent on IL12, indicating that IL7 also stimulates accessory cell function, leading to T cell activation.

Conclusion: IL7 stimulates proinflammatory cytokine production of intra-articular CD4+ T cells and accessory cells from patients with RA. The correlation with measures of disease activity indicates that IL7 might substantially contribute to the perpetuation of Th1 and TNFα mediated proinflammatory responses in patients with RA.

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Selected References

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Figures and Tables

Figure 1
(A) Serum IL7 levels of patients with RA (n=34) compared with an age and sex matched healthy control group (n=32, HC). Mean (SEM) values are given. Patients with RA showed a significantly higher serum IL7 level than HC (p<0.05). (B) The serum ...
Figure 2
IL7 stimulates TNFα production by RA SFMC. SFMC (1x106/ml) were incubated without or with IL7 (10 ng/ml) for five days. Mean (SEM) values are given (n=4). Asterisks indicate significant difference compared with control culture (*p<0.05). ...
Figure 3
Effect of IL7 on cytokine production by RA synovial T cells. (A) SFMC (1x106/ml) were incubated with or without IL7 (10 ng/ml) for five days, followed by T cell-specific stimulation with CD3/CD28 for 24 hours. Secretion of TNFα, IFNγ, ...
Figure 4Figure 4
Effect of IL7 on cytokine production by synovial T cells. SFMC (1x106/ml) from patients with RA were incubated with or without IL7 (10 ng/ml) for five days, followed by specific T cell stimulation with CD3/CD28 for 24 hours. Cytokine production during ...
Figure 5
(A) Expression of the IL7 receptor α chain (CD127) on isolated synovial CD4+ T cells (black histogram) compared with control staining (open histogram). (B) Isolated CD4+ T cells (5x105/ml) were stimulated with CD3/CD28 in the absence or presence ...
Figure 6
Effect of IL12 neutralising antibodies (aIL12) on IL7-stimulated cytokine production by RA synovial T cells. SFMC (1x106/ml) were incubated without (open bars) or with IL7 (10 ng/ml, black bars) and IL12 neutralising antibodies (5 µg/ml, grey ...

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