Tyrrell-Price, Jonathan;
(2003)
The effect of interleukin-10 and of interleukin-12 on the anti-double-stranded DNA antibody production by the blood lymphocytes of patients with systemic lupus erythematosus.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The effect of interleukin-10 and of interleukin-12 on the anti-double stranded DNA antibody production by the blood lymphocytes of patients with systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease, characterised by B-cell hyperactivity and the presence of various autoantibodies. Anti-double stranded DNA antibodies (anti-dsDNA antibodies) are thought to be important in SLE pathogcnisis as their serum titre often correlates with disease activity and they have been shown to induce lupus-like organ damage in many experimental models. If anti-dsDNA antibodies in patients with SLE were pathogenic, then the immune signals responsible for their expansion could be responsible for inducing disease flare. The cytokines interleukin-10 (IL-10) and interleukin-12 (IL-12) regulate antibody production in other systems and the levels of both of these cytokines arc related to disease activity in SLE. Serum levels of IL-10 conelate positively with disease activity and the in vitro production of IL-12 correlates negatively with disease activity, moreover this deficit in IL-12 production is due to IL-10 overproduction. This observation raises the possibility that the imbalance between these two cytokines might be involved in anti-dsDNA antibody production. Cultures of blood mononuclear cells from SLE patients with different disease activities were treated with IL-10 or IL-12 and the resulting supernatants tested for their antibody production by ELISA; both cross-sectional and longitudinal studies were earned out. The results showed that the effect of IL-10 on antibody production varied with disease activity. Further experiments using depleted cell populations revealed that T-cells, but not monocytes, played a role in determining the effects of IL-10. Parallel experiments utilising flow cytometry revealed that IL-10 may exert some of its T-cell dependent effects on antibody production through the induction of apoptosis. IL-12 both increased and decreased anti-dsDNA antibody production and a number of different factors, including disease activity and inter-patient variation might be responsible for this. These findings are consistent with the role of IL-10 in the regulatory suppression of immune responses. The effect of IL-12 requires further examination.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The effect of interleukin-10 and of interleukin-12 on the anti-double-stranded DNA antibody production by the blood lymphocytes of patients with systemic lupus erythematosus |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Health and environmental sciences; Systemic lupus erythematosus |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10101365 |
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