Interleukin-6 (IL-6) in adjuvant arthritis of rats and its pharmacological modulation

Theisen-Popp, P; Pape, H. C.; Müller‐Peddinghaus, R.

doi:10.1016/0192-0561(92)90117-4

Cited by 38 publications

(22 citation statements)

References 23 publications

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“…Inhibition of COX-2 activity also reversed systemic IL-6 production in arthritic animals, suggesting that PGs provide a costimulatory signal for both local and systemic IL-6 production in adjuvant arthritis. Partial inhibition of systemic IL-6 production by treatment with indomethacin has been documented previously (38). Both enhancement and suppression of TNF-␣ production have been demonstrated to be dose dependently regulated by PGE 2 and cAMP in rat peritoneal macrophages (39), but we observed no significant change in the level of TNF-␣ mRNA in the paws of rats treated with SC-58125 or indomethacin.…”

Section: Discussioncontrasting

confidence: 50%

Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.

Anderson¹,

Hauser²,

McGarity³

et al. 1996

J. Clin. Invest.

533

320

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Prostaglandins formed by the cyclooxygenase (COX) enzymes are important mediators of inflammation in arthritis. The contribution of the inducible COX-2 enzyme to inflammation in rat adjuvant arthritis was evaluated by characterization of COX-2 expression in normal and arthritic paws and by pharmacological inhibition of COX-2 activity. The injection of adjuvant induced a marked edema of the hind footpads with coincident local production of PGE 2 . PG production was associated with upregulation of COX-2 mRNA and protein in the affected paws. In contrast, the level of COX-1 mRNA was unaffected by adjuvant injection. TNF-␣ and IL-6 mRNAs were also increased in the inflamed paws as was IL-6 protein in the serum. Therapeutic administration of a selective COX-2 inhibitor, SC-58125, rapidly reversed paw edema and reduced the level of PGE 2 in paw tissue to baseline. Interestingly, treatment with the COX-2 inhibitor also reduced the expression of COX-2 mRNA and protein in the paw. Serum IL-6 and paw IL-6 mRNA levels were also reduced to near normal levels by SC-58125. Furthermore, inhibition of COX-2 resulted in a reduction of the inflammatory cell infiltrate and decreased inflammation of the synovium. Notably, the antiinflammatory effects of SC-58125 were indistinguishable from the effects observed for indomethacin. These results suggest that COX-2 plays a prominent role in the inflammation associated with adjuvant arthritis and that COX-2 derived PGs upregulate COX-2 and IL-6 expression at inflammatory sites. ( J. Clin. Invest. 1996. 97:2672-2679.)

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Section: Discussioncontrasting

confidence: 50%

Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.

Anderson¹,

Hauser²,

McGarity³

et al. 1996

J. Clin. Invest.

533

320

View full text Add to dashboard Cite

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“…In adjuvantinduced arthritis, the acute response to antigens is correlated with the presence of IL-1 and TNF, whereas IL-6 is involved in the systemic and local events underlying adjuvant arthritis, especially in the later phase (36). IL-6 has been reported to be a good marker of arthritis, including adjuvant-induced arthritis (37) and rheumatoid arthritis (4). A high correlation between IL-6 in serum and in synovial fluid and the severity of chronic arthritis in rats has been reported (5).…”

Section: Discussionmentioning

confidence: 98%

Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats

Granado¹,

Priego²,

Martín³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

155

121

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Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01) and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells.

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“…Whilst clear elevations of serum IL-6 have been previously observed in human RA [35,36] and experimental arthritides including AIA [20,[37][38][39], elevated levels of IL-1 protein have been described in adjuvant arthritis [40], and, at least in some studies, in human RA [41,42], but not in AIA [39]. Although the role of systemic elevation of IL-1 and IL-6 in AIA is presently unclear, evidence for a systemic proinflammatory influence of IL-6 on AIA has recently been reported in IL-6 knock-out mice [43].…”

Section: Cytokine Profile During Acute Aiamentioning

confidence: 96%

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

Simon

Surber

Kleinstäuber

et al. 2001

Journal of Autoimmunity

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Interleukin-6 (IL-6) in adjuvant arthritis of rats and its pharmacological modulation

Cited by 38 publications

References 23 publications

Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.

Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.

Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

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