Effects of salbutamol on the inflammatory parameters and angiogenesis in the rat air pouch model of inflammation

Tahereh Eteraf-Oskouei, Arezu Akbarzadeh‐Atashkhosrow, Milad Maghsudi, Moslem Najafi

Abstract


In the present study, effects of salbutamol on the inflammatory parameters, angiogenesis, interleukin-1 beta (IL-1β) and vascular endothelial growth factor (VEGF) levels were investigated in an air pouch model of inflammation. Inflammation was induced by intrapouch administration of 1% solution of sterile carrageenan in male Wistar rats. Salbutamol (125, 250 and 500 µg/rat) and salbutamol (500 µg/rat) plus propranolol (100 µg/rat) were injected intrapouch. After 6 and 72 h, fluid inside the pouches was collected to measure volume of exudates, leukocytes number and IL-1β levels. To determine angiogenesis, the granulation tissues were dissected out and weighed 3 days after carrageenan injection, then hemoglobin concentration was assessed using a hemoglobin assay kit. In addition, amount of VEGF in the exudates was measured 72 h after induction of inflammation. Leukocyte accumulation and the volume of exudates were significantly inhibited by salbutamol administration. In addition, salbutamol decreased the production of VEGF and IL-1β. Moreover, all used doses of salbutamol significantly inhibited angiogenesis. Interestingly, effects of salbutamol on the attenuation of angiogenesis and inflammatory parameters was similar to diclofenac sodium. Co-administration of propranolol with salbutamol clearly reversed anti-inflammatory effects of salbutamol. Salbutamol can decrease acute and chronic inflammation by β2-adrenergic receptors activation. The observed IL-1β and VEGF inhibitory properties of salbutamol may be responsible for anti-inflammatory and anti-angiogenic effect of the agent.


Keywords


Salbutamol; Inflammation; Angiogenesis; Air pouch; Carrageenan; VEGF; IL-1β

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References


Serafeim A, Gordon J. The immune system gets nervous. Curr Opin Pharmacol. 2001;1(4): 398-403.

Prenner BM. Role of long-acting beta2-adrenergic agonists in asthma management based on updated asthma guidelines. Curr Opin Pulm Med. 2008;14(1):57-63.

Zhang W, Fievez L, Cheu E, Bureau F, Rong W, Zhang F, et al. Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats. Eur J Pharmacol. 2010;628(1-3):171-178.

Uzkeser H, Cadirci E, Halici Z, Odabasoglu F, Polat B, Yuksel TN, et al. Anti-inflammatory and antinociceptive effects of salbutamol on acute and chronic models of inflammation in rats: involvement of an antioxidant mechanism. Mediators Inflamm. 2012;2012:438912.

Kvien TK. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics. 2004;22(1):1-12.

Dalmarco EM, Astolfi G, de Liz R, de Córdova CM, Fröde TS. Modulatory effect of mycophenolate mofetil on carrageenan-induced inflammation in the mouse air pouch model. Int Immunopharmacol. 2012;13(4):476-482.

Martin SW, Stevens AJ, Brennan BS, Davies D, Rowland M, Houston JB. The six-day-old rat air pouch model of inflammation: Characterization of the inflammatory response to carrageenan. J Pharmacol Toxicol Methods. 1994. 32(3):139-147.

Edwards JC, Sedgwick AD, Willoughby DA. The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J Pathol. 1981.134(2):147-156.

Sato K, Komatsu N, Higashi N, Imai Y, Irimura T. Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1. Clin Immunol. 2005;115:47-50.

Colville-Nash P, Lawrence T. Air-pouch models of inflammation and modifications for the study of granuloma-mediated cartilage degradation. Methods Mol Biol. 2003;225: 181-189.

Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9(6):653-660.

Colville-Nash PR. Scott DL. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications. Ann Rheum Dis. 1992;51(7):919-925.

Paleolog EM. Angiogenesis in rheumatoid arthritis. Arthritis Res. 2002;4:S81-S90.

Clavel G, Bessis N, Boissier MC. Recent data on the role for angiogenesis in rheumatoid arthritis. Joint Bone Spine. 2003;70(5):321-326.

Clavel G, Valvason C, Yamaoka K, Lemeiter D, Laroche L, Boissier MC, et al. Relationship between angiogenesis and inflammation in experimental arthritis. Eur Cytokine Netw. 2006;17(3):202-210.

Makhni E. Angiogenesis: An Examination of both Tumorigenic and Rehabilitative Properties. MIT Undergrad Res J. 2003; 8:23-26.

Kubota Y. Tumor angiogenesis and anti-angiogenic therapy. Keio J Med. 2012;61(2):47-56.

Kavelaars A. Regulated expression of alpha-1 adrenergic receptors in the immune system. Brain Behav Immun. 2002;16(6):799-807.

Lorton D, Lubahn C, Bellinger DL. Potential use of drugs that target neural-immune pathways in the treatment of rheumatoid arthritis and other autoimmune diseases. Curr Drug Targets Inflamm Allergy. 2003;2(1):1-30.

Lane T, Lachmann HJ. The emerging role of interleukin-1beta in autoinflammatory diseases. Curr Allergy Asthma Rep. 2011;11(5):361-368.

Dinarello CA. Interleukin-1β and the Autoinflammatory Diseases. New Engl J Med. 2009;360(23):2467-2470.

Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Annu Rev Med, 2014;65:223-244.

Appleton I, Brown NJ, Willis D, Colville-Nash PR, Alam C, Brown JR, et al. The role of vascular endothelial growth factor in a murine chronic granulomatous tissue air pouch model of angiogenesis. J Pathol. 1996;180(1):90-94.

Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol. 2001;106(4):148-156.

Sedgwick AD, Sin YM, Edwards JC, Willoughby DA. Increased inflammatory reactivity in newly formed lining tissue. J Pathol. 1983;141(4):483-495.

Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: carrageenan air pouch. Curr Protoc Pharmacol. 2012. Chapter 5: Unit.5.6.

Ajoy Kumar Ghosh A, Hirasawa N, Ohtsu H, Watanabe T, Ohuchi K. Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. J Exp Med, 2002;195(8):973-982.

del Rey A, Besedovsky HO. Sympathetic nervous system-immune interactions in autoimmune lymphoproliferative diseases. Neuroimmuno-modulation. 2008;15(1):29-36.

Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-435.

Sun L, Ye RD. Role of G protein-coupled receptors in inflammation. Acta Pharmacol Sin. 2012;33(3):342-350.

Voronov E, Carmi Y, Apte RN. Role of IL-1-mediated inflammation in tumor angiogenesis. Adv Exp Med Biol. 2007;601:265-270.

Johnson JD, Cortez V, Kennedy SL, Foley TE, Hanson H, Fleshner M. Role of central beta-adrenergic receptors in regulating proinflammatory cytokine responses to a peripheral bacterial challenge. Brain Behav Immun. 2008;22(7): 1078-1086.

Hallsworth MP, Twort CH, Lee TH, Hirst SJ. Beta(2)-adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells. Br J Pharmacol. 2001;132(3):729-741.

Naldini A, Carraro F. Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy. 2005;4(1):3-8.

Szekanecz Z, Besenyei T, Paragh G, Koch AE. New insights in synovial angiogenesis. Joint Bone Spine. 2010;77(1):13-19.

Stati T, Musumeci M, Maccari S, Massimi A, Corritore E, Strimpakos G, et al. beta-blockers promote angiogenesis in the mouse aortic ring assay. J Cardiovasc Pharmacol. 2014;64(1):21-27.

Lu J, Kasama T, Kobayashi K, Yoda Y, Shiozawa F, Hanyuda M, et al. Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis. J Immunol. 2000;164(11): 5922-5927.


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