Effect of IL-10 on collagen-induced arthritis in mice

Tanaka, Yosuke; Otsuka, Takeshi; Hotokebuchi, Takao; Miyahara, Hisaaki; Nakashima, Hitoshi; Kuga, Seiji; Nemoto, Yoshiaki; Niiro, Hiroaki; Niho, Yoshiyuki

doi:10.1007/bf02280992

Cited by 82 publications

(45 citation statements)

References 30 publications

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“…It has been reported that there was an increase in the IgG1:IgG2a ratio after injection of vIL-10-expressing vectors (17), and a decrease in total anti-CII IgG was observed after repeated high doses of murine rIL-10 in rats (14). However, others did not see any such effects when using similar systems (15,16,18,58,60). These discrepancies could perhaps be explained by the dose and timing of IL-10 treatment, indicating that much more effort must be put in to investigate how variations in IL-10 levels affect different functions of the immune system.…”

Section: Discussionmentioning

confidence: 97%

IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

Johansson

Hansson

Nandakumar

et al. 2001

The Journal of Immunology

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IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and collagen-induced arthritis (CIA). In this study, we investigated how IL-10 deficiency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10−/− mice had an 8-cM 129/Ola fragment around the IL-10 gene. The mice were treated with antibiotics, appeared healthy, and had no colitis. T cells from IL-10−/− mice expressed similar levels of IFN-γ, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-α production compared with IL-10+/− littermates. IL-10−/− mice had an increased incidence, and a more severe CIA disease than the IL-10+/− littermates. To study the role of IL-10 in T cell tolerance, IL-10−/− were crossed into mice carrying the immunodominant epitope, CII(256–270), in cartilage (MMC) or in skin (TSC). Both IL-10−/− and IL-10+/− MMC and TSC mice were completely tolerized against CIA, indicating that lack of IL-10 in this context did not break tolerance. To investigate whether IL-10 was important in the effector phase of CIA, arthritis was induced with anti-CII Abs. Surprisingly, IL-10−/− were less susceptible to Ab-transferred arthritis, as only 30% showed signs of disease compared with 90% of the littermates. Therefore, IL-10 seemed to have a protective role in CIA, but seemed to exacerbate the arthritogenicity of anti-CII Abs. These data emphasize the importance of studying IL-10 in a defined genetic context in vivo, to understand its role in a complex disease like arthritis.

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Section: Discussionmentioning

confidence: 97%

IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

Johansson

Hansson

Nandakumar

et al. 2001

The Journal of Immunology

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“…Several lines of evidence suggest that GLAST and GLT-1 are the predominant GTs and are responsible for clearing synaptic glutamate and preventing excitotoxicity (Tanaka et al, 1996;Robinson and Dowd, 1997). Previous study has shown that many regulatory factors, such as dibutyryl cAMP, epidermal growth factor, and pituitary adenylate cyclase-activating polypeptide, modulate GLAST and GLT-1 mRNA levels (Zelenaia and Robinson, 2000).…”

Section: Discussionmentioning

confidence: 99%

Ultra-Low-Dose Naloxone Restores the Antinociceptive Effect of Morphine and Suppresses Spinal Neuroinflammation in PTX-Treated Rats

Tsai

Jang

Tai

et al. 2008

Neuropsychopharmacol

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The aim of the present study was to examine the effect of ultra-low-dose naloxone on pertussis toxin (PTX)-induced thermal hyperalgesia in rats and its underlying mechanisms. Male Wistar rats, implanted with an intrathecal catheter with or without a microdialysis probe, received a single intrathecal injection of PTX (1 mg in 5 ml saline). Four days after PTX injection, they were randomly given a different dose of naloxone (either 15 mg or 15 ng in 5 ml saline), followed by a morphine injection (10 mg in 5 ml saline) after 30 min. The results found that PTX injection induced thermal hyperalgesia and increasing excitatory amino acid (EAA; L-glutamate and L-aspartate) concentration in the spinal CSF dialysates. Ultra-low-dose naloxone not only preserved the antinociceptive effect of morphine but also suppressed the PTX-evoked EAA release as well. Moreover, ultra-low-dose naloxone plus morphine administration inhibited the downregulation of L-glutamate transporters (GTs) and the L-glutamate-metabolizing enzyme glutamine synthetase (GS), and, moreover, inhibited microglial activation and suppressed cytokine expression in PTX-treated rat spinal cords. These results show that ultra-low-dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms include (a) inhibition of pro-inflammatory cytokine expression, (b) attenuation of PTX-evoked EAA release, and (c) reversion of the downregulation of GT expression.

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“…In many cases, their precise roles are, as yet, incompletely defined. A growing body of evidence from both animal models of arthritis and human RA suggests that Th2-type cytokines, such as IL-4 and IL-10, can protect against arthritis, whereas Th1-type cytokines, such as IL-2 and IFN-␥, can be pro-inflammatory (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Heterogeneous Effects Of Il-2 Onmentioning

confidence: 99%

Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

Thornton

Boivin

Kim

et al. 2000

The Journal of Immunology

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IL-2 is generally considered a pro-inflammatory cytokine that exacerbates Th1-mediated disease states, such as autoimmune arthritis. Consistent with this role for IL-2, recent studies from our laboratory demonstrate that IL-2 mRNA is markedly increased during the acute stage of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. To further define the role of IL-2 in CIA, the levels of IL-2 protein and its receptor and the effects of IL-2 administration were analyzed during CIA. IL-2 protein and IL-2R were preferentially expressed at disease onset, compared with later stages of disease. Administration of recombinant human IL-2 (rhIL-2) at, or just before, disease onset exacerbated disease; surprisingly, rhIL-2 given before disease onset inhibited CIA, associated with reduced cellular and humoral responses to type II collagen. Determination of in vivo serum levels of Th1 and Th2 cytokines in response to rhIL-2 treatment demonstrated that IFN-γ, but not IL-4, was markedly up-regulated in response to IL-2. In mice treated with anti-IFN-γ Ab, both early and late IL-2 administration exacerbated CIA. Thus, IL-2 can have two opposite effects on autoimmune arthritis, a direct stimulatory effect and an indirect suppressive effect that is mediated by IFN-γ.

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Effect of IL-10 on collagen-induced arthritis in mice

Cited by 82 publications

References 30 publications

IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies

Ultra-Low-Dose Naloxone Restores the Antinociceptive Effect of Morphine and Suppresses Spinal Neuroinflammation in PTX-Treated Rats

Heterogeneous Effects of IL-2 on Collagen-Induced Arthritis

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