The Impact of Gender on the Inflammatory Parameters and Angiogenesis in the Rat Air Pouch Model of Inflammation

Document Type: Original Article


1 School of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

2 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Pharmacology and Toxicology, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

4 Research Center for Pharmaceutical Nanotechnology, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran


Air pouch is a well-established inflammatory model in which fluid extravasations; leukocyte migration, angiogenesis and other parameters involved in the inflammatory response can be measured. In this study, the influence of gender on inflammatory parameters has been examined in the air pouch model.
Materials and Methods
To induce air pouch, adult male and female Wistar rats were anesthetized, then 20 ml and 10 ml of sterile air were injected subcutaneously on the back on day 0 and day 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 6 and 72 hr, the rats were sacrificed, pouch fluid was collected in order to determine exudates volume and the accumulated cells were counted using a hemocytometer. Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using hemoglobin kit.
Analysis of our data demonstrated a sexually dimorphic pattern in inflammation parameters both in acute and chronic forms (P<0.05). The value of angiogenesis in the air pouch model in male rat was higher than that female rats (P<0.001).
The degree of inflammation and angiogenesis induced in Wistar rat air pouch model is gender-dependent, suggesting that gender may be a key consideration in the design of inflammation experiments.


1.Da Silva JA. Sex hormones and glucocorticoids: interactions with the immune system. Ann NY Acad Sci 1999; 876:102-117.

2.Joe B, Garrett MR, Dene H, Remmers EF, Meng H. Genetic susceptibility to carrageenan-induced innate inflammatory response in inbred strains of rats. Eur J Immunogenet 2003; 30:243-247.

3.Sedgwick AD, Moore AR, Al-Duaij A Y, Edwards JC, Willoughby DA. The mmune response to pertussis in the 6-day air pouch: a model of chronic synovitis. Br J Exp Pathol 1985; 4:455-464.

4.Gambero A, Becker TL, Gurgueira SA, Benvengo YHB, Ribeiro ML, Mendonca S, et al. Acute inflammatory response induced by Helicobacter pylori in the rat air pouch. FEMS Immunol Med Microbiol 2003; 38:193-198.

5.Ghosh AK,Hirasawa N,Niki H,Ohuchi K.Cyclooxygenase-2-mediated angiogenesis in carrageenin-induced granulation tissue in rats. J Pharmacol Exp Ther 20002; 95:802-809.

6.Colville-Nash P, Lawrence T. Air-pouch models of inflammation and modifications for the study of granuloma- mediated cartilage degradation. In: Winyard PG,Willoughby DA.Methods in Molecular Biology. London: The William Harvey Research Institute; 2003.p.181-189.

7.Ghosh AK, Hirasawa N, Ohtsu H. Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. J Exp Med 2002; 195: 973-982.

8.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; 32:139-147.

9.Delano Dl, Montesinos MC, D’Eustachio P, Wiltshire T, Cronstein BN. An interaction between genetic factors and gender determines the magnitude of the inflammatory response in the mouse air pouch model of acute inflammation. Inflammation 2005; 29:1.

10.Crockett ET, Spielman W, Dowlatshahi Sh , He J. Sex differences in inflammatory cytokine production in hepatic ischemia-reperfusion. J Inflamm 2006; 3:16.

11.Sinha I, Cho BS, Roelofs KJ, Stanley JC, Henke PK, Upchurch GR. Female gender attenuates cytokine and chemokine expression and leukocyte recruitment in experimental rodent abdominal aortic aneurysms. Ann N Y Acad Sci 2006; 1085:367-379.

12.Barker LA, Dazin PF, Levine JD, Green PG. Sympathoadrenal-dependent sexually dimorphic effect of nonhabituating stress on in vivo neutrophil recruitment in the rat. Br J Pharmacol 2005; 145:872-879.

13.Hermes GL, Rosenthal L, Montag A, McClintock MK. Social isolation and the inflammatory response: sex differences in the enduring effects of a prior stressor. Am J Physiol Regul Integr Comp Physiol 2006; 290:R273- 282.

14.Lindhe J, Sonesson B.The effect of sex hormones on inflammation. I. The effect of a progestogen. J Periodontal Res 1966; 1:212-217.

15.Kemp SW, Reynolds AJ, Duffy LK. Gender differences in baseline levels of vascular endothelial growth factor in the plasma of alaskan sled dogs American. J Biochem and Biotech 2005; 2:111-114.