Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus

Llórente, Luis; Richaud‐Patin, Yvonne; García-Padilla, Carlos; Claret, Emmanuel; Jakez‐Ocampo, Juan; Cardiel, Mario H; Alcocer‐Varela, Jorge; Grangeot-Keros, L.; Alarcón‐Segovia, Donato; Wijdenes, John; Galanaud, Pierre; Émilie, Dominique

doi:10.1002/1529-0131(200008)43:8<1790::aid-anr15>3.0.co;2-2

Cited by 424 publications

(173 citation statements)

References 42 publications

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“…For example, continuous administration of anti-IL-10 delays onset of autoimmunity in (NZW ϫ NZB)F 1 mice, an effect perhaps mediated by up-regulation of TNF-␣ production (22). Moreover, it has been recently reported that anti-IL-10 administration to six human lupus patients with active disease, and dependent upon steroids for treatment, led to a reduction in disease activity (23).…”

Section: Il-10 Regulates Murine Lupusmentioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

210

175

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MRL/MpJ-Tnfrsf6lpr (MRL/MpJ-Faslpr; MRL-Faslpr) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10−/−) MRL-Faslpr (MRL-Faslpr IL-10−/−) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Faslpr IL-10+/− and MRL-Faslpr IL-10+/+ mice, respectively). MRL-Faslpr IL-10−/− mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Faslpr IL-10−/− mice was closely associated with enhanced IFN-γ production by both CD4+ and CD8+ cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Faslpr animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus.

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Section: Il-10 Regulates Murine Lupusmentioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

210

175

View full text Add to dashboard Cite

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“…In vitro, interleukin-10 blockade corrects impaired cellular immune responses of SLE patients [127], suggesting that anti-IL-10 antibodies might represent a meaningful therapeutic approach in this disease. Indeed, clinical trials already tested murine anti-IL-10 for treatment of lupus erythematosus during 3 weeks [128]. This treatment resulted in rapid and long-lasting amelioration of the disease.…”

Section: Il-10mentioning

confidence: 99%

Structure and function of interleukin-22 and other members of the interleukin-10 family

Trivella

Ferreira-Junior

Dumoutier

et al. 2010

Cell. Mol. Life Sci.

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The IL-10 family of cytokines is comprised of IL-10, . The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.

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“…Antagonists of IL-10 or TGF-b may contribute to greater efficacy of TLR-agonist therapy in several ways. Given that both cytokines can inhibit the activation of NF-kB (Heyen et al, 2000;Le et al, 2004), antibodies (Llorente et al, 2000) or small molecules (Saunier and Akhurst, 2006) directed against these cytokines or their receptors should be able to increase the strength of TLR signaling in tumor cells. In addition, inhibiting these cytokines should enhance anti-tumor T-cell responses since IL10 and TFG-b are made by TLRactivated regulatory T cells (Curiel, 2007).…”

Section: Strategies To Improve the Efficacy Of Tlr Agonists In Hematomentioning

confidence: 99%

Obstacles to effective Toll-like receptor agonist therapy for hematologic malignancies

et al. 2008

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Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus

Abstract: This is the first report of IL-10 antagonist administration to humans. The study shows the involvement of IL-10 in the pathogenesis of SLE, and indicates that the use of IL-10 antagonists may be beneficial in the management of refractory SLE.

Cited by 424 publications

References 42 publications

IL-10 Regulates Murine Lupus

IL-10 Regulates Murine Lupus

Structure and function of interleukin-22 and other members of the interleukin-10 family

Obstacles to effective Toll-like receptor agonist therapy for hematologic malignancies

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