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. 1997 Jun;56(6):364–368. doi: 10.1136/ard.56.6.364

Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice

I Campbell 1, A Bendele 1, D Smith 1, J Hamilton 1
PMCID: PMC1752394  PMID: 9227165

Abstract

OBJECTIVE—To examine the effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on disease progression in the collagen induced arthritis (CIA) model in mice.
METHODS—DBA/1 mice were primed for a suboptimal CIA response by intradermal injection of chick type II collagen without a secondary immunisation. Three weeks after immunisation the mice were given four to five consecutive daily intraperitoneal injections of recombinant murine GM-CSF (15 µg; 5 × 105 U), or vehicle, and arthritis development was monitored by clinical scoring of paws and calliper measurements of footpad swelling. At approximately six to eight weeks after immunisation mice were killed, their limbs removed and processed for histological analyses of joint pathology.
RESULTS—Control animals receiving a single immunisation with collagen exhibited a varied CIA response both in terms of incidence and severity. Mice treated with GM-CSF at 20 to 25 days after immunisation with collagen had a consistently greater incidence and more rapid onset of disease than the vehicle treated control mice, based on clinical assessment. GM-CSF treated mice showed higher average clinical scores and greater paw swelling than controls. Histological analyses of joints reflected the clinical scores with GM-CSF treated mice displaying more pronounced pathology (synovitis, pannus formation, cartilage and bone damage) than control mice.
CONCLUSION—GM-CSF is a potent accelerator of the pathological events leading to chronic inflammatory polyarthritis in murine CIA supporting the notion that GM-CSF may play a part in inflammatory polyarthritis, such as rheumatoid arthritis.



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Figure 1  .

Figure 1  

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Kinetics of the effect of GM-CSF on clinical score and paw swelling in CIA. Mice were immunised with chick CII and 20 to 23 days later (experiment 2 from table 1) were given daily ip injections of either 15 µg GM-CSF or vehicle (control). Arthritis development was assessed every two to three days by (A) a clinical score (maximum score 12 per mouse) and (B) by calliper measurement of the hind footpad thickness. Results show the means (SEM) for 10 mice per group. For (B) the paw sizes of each individual limb were expressed as a percentage of their day 20 values and the mean (SEM) were then obtained for the 20 limbs.

Figure 2  .

Figure 2  

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Medial aspect of knee joint from type II collagen immunised mouse treated at days 21 to 25 by ip injection of 15 µg GM-CSF (experiment 1 from table 1). Pronounced loss of proteoglycan from the tibial articular cartilage is evident by the loss of intense staining (arrow) while the adjacent femoral cartilage is eroded down to the calcified cartilage layer (darker stain). The synovium (arrow head) is markedly thickened as a result of infiltration by inflammatory cells and proliferation of synovial cells and has invaded into the bone. Toluidine blue, frontal section, original magnification ×100.

Figure 3  .

Figure 3  

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Histological assessment of CIA in mice treated with and without GM-CSF. Mice were immunised with chick CII and 21 to 25 days later were given daily ip injections of either 15 µg GM-CSF or vehicle (control). At 45 days after immunisation the mice were killed, their limbs removed, and the joints (fore paw, knee, ankle, and hind paw) were fixed, decalcified, embedded in paraffin wax, and 5 µm sections prepared and stained with haematoxylin and eosin. The joints were evaluated for the histological changes of inflammation, pannus formation, cartilage damage, and bone damage, each on a scale of 0 to 5. Results express the mean (SEM) for 10 mice per group. Joints from GM-CSF treated mice scored significantly higher (p < 0.05, Mann-Whitney two sample test) than the control for each parameter.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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