Cytokine abnormalities in human lupus

Linker‐Israeli, Mariana

doi:10.1016/0090-1229(92)90084-2

Cited by 89 publications

(65 citation statements)

References 12 publications

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“…We assessed spontaneous cytokine production by B cells and monocytes in patients with lupus or rheumatoid arthritis and in normal donors and showed that IL-6 production was significantly enhanced in lupus, compared to the other two donor groups, confirming previous findings by other investigators [1][2][3][4][5][6][7][8][9]. In addition, we found a direct correlation between secreted IL-6 levels in lupus B-cell/monocyte supernatants and the levels of TNF-a, while other cytokines such as IL-1 and GM-CSF were only detected in the presence of high levels of TNF-a.…”

Section: Discussionsupporting

confidence: 87%

“…A number of studies have demonstrated increased IL-6 production in SLE, which could play a role in the enhancement of B-cell differentiation in this condition [1][2][3][4][5][6][7][8][9][10][11][12]. IL-6 is one of several cytokines including TNF-a and GM-CSF, whose secretion is inhibited by IL-10 and so the possibility exists that enhanced IL-6 secretion in SLE is the result of either reduced IL-10 production or deficient IL-10 responsiveness [13].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated increased levels of circulating interleukin-6 (IL-6) in systemic lupus erythematosus (SLE), or have found either enhanced production of this cytokine in vitro by mononuclear cells from lupus patients, or hyperactive B-cell responses to this cytokine [1][2][3][4][5][6][7][8][9][10][11][12]. Major sources of IL-6 are monocytes/macrophages and B cells.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin‐10 Response Abnormalities in Systemic Lupus Erythematosus

Mongan¹,

Ramdahin

Warrington

1997

Scand J Immunol

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It has been previously reported that the production of interleukin‐6 (IL‐6) is often enhanced in systemic lupus erythematosus (SLE). The authors examined the secretion of IL‐6, tumour necrosis factor‐α (TNF‐α), granulocyte–macrophage colony‐stimulating factor, IL‐1α and IL‐4 by B cells and monocytes from lupus patients and compared this to the production in normal controls and in rheumatoid arthritis patients. IL‐6 production was increased an average of 3.4‐fold compared to that in normal subjects and 8.4‐fold compared to rheumatoid arthritis patients. In SLE, a strongly positive correlation was found between the levels of IL‐6 and TNF‐α (R = 0.8987, P = 0.002). Since production of both IL‐6 and TNF‐α is regulated by IL‐10, the enhancement of the production of these cytokines could reflect a defect in either IL‐10 production or responsiveness. However, spontaneous production of IL‐10 was enhanced in cultures of B cells and monocytes from lupus patients, compared to normal controls, the levels being increased 3.1‐ to 6‐fold for monocytes and B cells, respectively. The finding of increased secretion of these cytokines implies an abnormality in IL‐10‐mediated suppression in SLE. To assess this possibility, the authors examined recombinant human IL‐10‐mediated suppression of IL‐6 production by monocytes and B cells from lupus patients, compared to normal controls, and found that whereas IL‐10 caused a concentration‐dependent suppression of IL‐6 production in normal B cells and monocytes, this suppression was deficient in B cells and monocytes from lupus patients. In SLE, it therefore appears that there may be an intrinsic defect in IL‐10‐induced suppression of cytokine synthesis. This could explain the increased levels of IL‐10 and IL‐6 found in this condition, and may also be responsible for the characteristic polyclonal B‐cell activation that is seen.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interleukin‐10 Response Abnormalities in Systemic Lupus Erythematosus

Mongan¹,

Ramdahin

Warrington

1997

Scand J Immunol

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“…It has been shown that a low percentage of the T cells are activated in SLE patients (54). Moreover, the production of interleukin-2 and interferon-␥ is significantly decreased in SLE T cells compared with normal cells (57,58). Also, the fact that down-regulation of p16 correlates with down-regulation of the p21 and p23 phosphorylated forms as well as chain mRNA in SLE patients suggests that the abnormal TCR chain expression profile is the consequence of "intrinsic" alterations in nonactivated SLE T cells and is not due to activation by autoantigens.…”

Section: Discussionmentioning

confidence: 84%

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Nambiar

Enyedy

Fisher

et al. 2002

Arthritis & Rheumatism

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“…18 and for review, see ref. 27) and in lymph nodes from lupus-prone mice (28). Recombinant IFNy has been shown to increase the secretion of anti-dsDNA-IgG/IgM in PBMC isolated from SLE patients (29), and neutralization of IFNy has been shown to inhibit the onset of glomerulonephritis in (NZB X NZW)F, mice (30).…”

Section: Discussionmentioning

confidence: 99%

Histone‐specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double‐stranded DNA antibody production

Voll

Roth

Girkontaitė

et al. 1997

Arthritis & Rheumatism

137

145

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Objective. To investigate whether histone‐specific T helper (Th) cells that are able to induce anti‐doublestranded DNA (anti‐dsDNA) antibodies can be isolated from patients with systemic lupus erythematosus (SLE) and to characterize the cytokine secretion pattern of such Th clones. Methods. Peripheral blood mononuclear cells from SLE patients and healthy donors were stimulated with autologous apoptotic cell material or purified histones, expanded with interleukin‐2 (IL‐2), and cloned by limiting dilution. Histone reactivity of clones was examined by histone‐specific proliferation and cytokine release. Cytokines were determined by enzyme‐linked immunosorbent assay (ELISA) and CTLL‐2 bioassay. Induction of anti‐dsDNA antibodies was measured in cocultures of autologous B cells and Th clones by ELISA. Results. Numerous histone‐specific T cell receptor (TCR) α/β+ Th clones were established from 2 of 3 patients with active SLE and from 1 of 2 healthy individuals. Most Th clones secreted IL‐2, interferon‐γ (IFNγ), and IL‐4, whereas some produced predominantly IL‐2 and lFNγ. Th clones that could stimulate the production of anti‐dsDNA antibodies were derived from SLE patients and from a healthy individual. Conclusion. Th cells specific for histones may play an important role in the pathogenesis of SLE by inducing autoantibodies to dsDNA. Both Th1 and Th2 cytokines may be involved in the pathogenesis of SLE. The presence of histone‐specific Th cells in a healthy individual indicates the importance of peripheral tolerance for preventing autoimmunity to nuclear antigens.

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Cytokine abnormalities in human lupus

Cited by 89 publications

References 12 publications

Interleukin‐10 Response Abnormalities in Systemic Lupus Erythematosus

Interleukin‐10 Response Abnormalities in Systemic Lupus Erythematosus

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Histone‐specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double‐stranded DNA antibody production

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