Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin‐10: Interferon‐γ–secreting cells in the peripheral blood

Abstract

Objective. To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = &), versus normal controls (n = 60). Methods. ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC).Results. T cells were the major source of interleukin-2 (IL-2), IL-4, and interferon-? (IFNy), whereas monocytes were the primary source of IL-6 and IL-10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFNy and IL-2 (P 5 0.03), while significantly more PBMC produced IL-6 and IL-10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL-lO:IFN.]csecreting cells (P < 0.001).Conclusion. SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine-secreting PBMC.Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by multiple immune abnormalities that culminate in the overproduction of pathogenic autoantibodies (1-4). T cells and the factors they produce have been implicated in the development of lupus in mice and humans (5-7).Two broad classes of cytokines have been identified. Interferon-y (IFN y) and interleukin-2 (IL-2)

IL-10 Regulates Murine Lupus

“…However, the role of IL-10 in the pathogenesis of lupus remains controversial. The abnormally elevated amounts of IL-10 detected in serum of patients with SLE (19,20) and the recent observation that anti-IL-10 therapy can down-modulate disease in such patients (23) suggest that this cytokine may promote disease.…”

“…Yet, IL-10 can be secreted by many cell types, with multiple biological effects (17). For example, IL-10 can inhibit IFN-␥ production and inflammatory responses (36) as well as promote B cell proliferation and Ab production (19). Accordingly, IL-10 may have multiple effects in lupus depending on the stage of the disease.…”

The genetics of systemic lupus erythematosus: putting the pieces together

“…99 Among SLE patients, the numbers of IL-10-producing cells are increased in the peripheral blood, resulting in these patients having an abundance of pathogenic autoantibodies. [100][101][102] Moreover, lupus-prone mice that are administered recombinant IL-10 develop accelerated autoimmune disease. 103 For these reasons, IL-10 is a possible candidate gene in lupus susceptibility.…”

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

“…8 Moreover, B cells and monocytes of SLE patients produce an increased amount of IL10 compared to non-affected individuals. 9,10 Besides its functional relevance, IL10 is an attractive positional candidate gene since it maps in 1q32, in a region homologous to a murine SLE susceptibility region (reviewed in Ref. 11).…”