Local Angioneogenetic Effect of Intramuscular Interleukin-8 Injection

Abstract

A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Angioneogenesis, which plays significant roles in a variety of physiological processes such as embryonic growth and wound healing, is strictly delimited and is finely tuned by a balance of proangiogenic and antiangiogenic factors. This study was conducted to investigate the angioneogenic effect of interleukin-8 (IL-8) administered intramuscularly. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Twelve New Zealand white rabbits were included in this study. A total daily dose of 4 micrograms (1 mcg/kg) of IL-8 was administered into the left (Group A) and saline solution into the right (Group B) gluteus maximus muscles of 6 rabbits for 6 days. The remaining 6 rabbits constituted the sham group (Group C). Gluteal muscle samples were obtained from injection sites in all groups and were stained with hematoxylin-eosin and immunohistochemically by using streptavidin biotin method with CD31 antibody. Avidin-biotin peroxidase method (LSAB) was used as secondary and binding antibody. Diaminobenzidine tetrahydrochloride (DAB) was used as chromogenic substance. In immunohistochemical staining with CD31, vascular channels covered with brown stained cells or cell clusters were considered and were counted as vascular network. R Re es su ul lt ts s: : Three subjects in Group A and one subject in Group B displayed findings of large muscle necrosis and regeneration. Vascular channel score was significantly higher in Group A (p=0.032) (Group A; median=12.5, min=6, max=16. Group B; median=5, min=4, max=13. Group C; median=4.5, min=4, max=13.) than in the other groups. C Co on nc cl lu us si io on n: : IL-8 chemokine family seems to stimulate angioneogenesis in rabbit skeletal muscles. This result is promising in terms of the possible therapeutic potential of IL-8. Daily administration at a dose of around 1 mcg/kg caused local tissue necrosis, hence use of alternative routes such as intraarterial administration must be investigated to avoid such complications. K Ke ey y W Wo or rd ds s: : Angioneogenesis; interleukin-8; skeletal muscle Ö ÖZ ZE ET T A Am ma aç ç: : Embriyonik büyüme ve yara iyileşmesi gibi bir dizi fizyolojik süreçte önemli rol oynayan anjiyogenez, proanjiyojenik ve antianjiyojenik faktörlerin birbirlerinden kesin çizgiler ile dengelenmesiyle ayrılmış ve hassas şekilde düzenlenmiştir. Bu çalışma, intramusküler olarak uygulanan interlökin-8 (IL-8)'in anjiyoneogenetik etkisini araştırmak için yapılmıştır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmada on iki adet Yeni Zelanda cinsi beyaz tavşan kullanıldı. Altı gün boyunca altı tavşanın sol gluteusuna 1 mcg/kg'dan toplam 4 mikrogram IL-8 (Grup A), sağ gluteusuna serum fizyolojik (Grup B) enjeksiyonu uygulandı. Diğer altı tavşan kontrol grubu idi (Grup C). Enjeksiyon uygulanan bölgelerden alınan gluteal kas örnekleri, Hemotoksilen-Eozin ve Streptavidin-biotin yöntemi kullanılarak CD31 antikoru ile immünohistokimyasal olarak boyandı. Avidin-biotin peroksidaz metodu (LSAB) ikincil ve bağla...

Investigation of the direct hepatic effects of intramuscular interleukin-8 injection in an experimental rabbit model

“…The protein, consisting of 72 amino acids in its mature form, is identified as a basic and heparin-binding protein [7,9,11,12]. IL-8 also exhibits chemotactic activities against T lymphocytes and basophils, as well as neutrophils in vitro [9,10].…”

“…The protein, consisting of 72 amino acids in its mature form, is identified as a basic and heparin-binding protein [7,9,11,12]. IL-8 also exhibits chemotactic activities against T lymphocytes and basophils, as well as neutrophils in vitro [9,10]. IL-8 production has also been observed in vitro in a wide variety of cells, including monocytes, T lymphocytes, neutrophils, vascular endothelial cells, dermal fibroblasts, keratinocytes, hepatocytes, and human gastric cancer cells [13].…”

“…However, IL-8 injection is not a currently used method. We conducted one of the few studies in the literature that focused on investigating the angioneogenic effect of IL-8 administered intramuscularly in rats, and concluded that daily administration at a dose of around 1 mcg/kg caused local tissue necrosis [9]. However, duration of repeat doses and safety dosage ranges must be clarified by further investigations.…”

“…For 6 days, 1 gluteus maximus muscle was injected daily with 1 mcg/kg (The dosages were standardized according to previous studies [9]) of IL-8 (BioVision recombinant human endothelial IL-8, cat. number 4149-25) in 6 rabbits (Group A).…”

“…IL-8 can be produced by a various types of involved in inflammation, including monocytes and endothelial cells. Furthermore, the effects of IL-8 in acute phase reaction, inflammatory response, and angiogenesis stimulation have already been determined [7,9]. Additionally, several observations suggest that IL-8 pathways might also be involved in the pathogenesis of chronic liver disease [3,5,6,10].…”