IGF-I and IGF-I-binding proteins in rats with adjuvant-induced arthritis given recombinant human growth hormone

Abstract

Adjuvant-induced arthritis in rats is associated with growth failure, hypermetabolism and accelerated protein breakdown. We have previously reported that adjuvant-induced arthritis in rats results in a decrease in body weight gain, pituitary GH mRNA, circulating GH and IGF-I together with an increase in serum IGF-binding proteins (IGFBPs). The aim of this study was to analyze the role of GH in the decrease in body weight and in the alterations in the IGF-I system observed in chronic inflammation.Male Wistar rats were injected with complete Freund's adjuvant and 16 days later arthritic rats were injected daily with recombinant human GH (rhGH) (3 IU/kg s.c.) for 8 days; control rats received 250 µl saline. Arthritis significantly decreased body weight gain and serum IGF-I. These decreases were not due to the reduced food intake, since in pair-fed rats they were not observed. Furthermore, administration of rhGH to arthritic rats increased body weight gain without modifying food intake. To further investigate the effect of GH administration, 14 days after adjuvant injection both control and arthritic rats were treated with 0, 1·5, 3 or 6 IU/kg of rhGH. GH treatment at the dose of 3 and 6 IU/kg significantly increased body weight gain in arthritic rats. GH administration, at the higher dose of 6 IU/kg, increased hepatic and serum concentrations of IGF-I in both control and arthritic rats. In control rats, rhGH at the three doses assayed increased circulating IGFBP-3. GH treatment in arthritic rats decreased IGFBP-1 and -2, and did not modify IGFBP-4. GH treatment at the dose of 3 IU/kg also decreased circulating IGFBP-3 in arthritic rats.These data suggest that GH treatment can ameliorate the catabolism observed in adjuvant-induced arthritis, an effect mediated, at least in part, by modifications in the circulating IGFBPs.

Arthritis-induced increase in serum levels of IGF-binding protein-3 in rats is secondary to the decrease in its proteolytic activity

“…The results showed that the high serum levels of IGFBP-3 in arthritic rats appear to be largely due to decreased proteolysis of IGFBP-3, since hepatic synthesis of IGFBP-3 was not changed. As we have already described in arthritic rats (Ibáñez de Cáceres et al 2000), concentrations of IGFBP-3 in serum are increased and GH treatment prevents this increase. These changes in serum protein concentrations did not correlate with the hepatic synthesis of IGFBP-3, since liver IGFBP-3 mRNA content was not modified by arthritis and the synthesis remained constant in response to GH.…”

“…We have previously observed an increase in serum IGFBP-3 in arthritic rats, and found that GH administration prevents this increase (Ibáñez de Cáceres et al 2000). Therefore, the aim of this work was to study the mechanism responsible for the increase in serum IGFBP-3 in arthritic rats, by evaluating hepatic synthesis and proteolysis of IGFBP-3 in the serum.…”

Comparison of the effects of the n-3 polyunsaturated fatty acid eicosapentaenoic and fenofibrate on the inhibitory effect of arthritis on IGF1

“…Arthritic rats have low serum IGF1 levels that are inversely related to body weight gain (López-Calderón et al 1999), whereas chronic GH administration to arthritic rats increases body weight and serum IGF1 levels (Ibañez de Cáceres et al 2000). Similarly, GH administration to juvenile RA patients increases growth (Touati et al 1998).…”

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

“…Adjuvant-induced arthritis is an animal model for chronic inflammation and rheumatoid arthritis characterized by a decrease in body weight and cachexia (Roubenoff et al 1997, Ibáñez de Cáceres et al 2000. Cachexia, which also prevails in other situations such as burns, sepsis and cancer, is characterized by anorexia and tissue wasting, reflected essentially in a loss of adipose tissue and skeletal muscle.…”