Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice

Abstract

Tissue eosinophilia is a feature of idiopathic inflammatory bowel disease and other forms of colonic inflammation but it is not clear whether the role of eosinophils in the disease process is to contribute to tissue damage. Interleukin 5 (IL-5) stimulates production and activation of eosinophils in vitro and enhances immunoglobulin A (IgA) production. As very little is known about the function of IL-5 in the colon, the aim of this study was to assess its role in colonic inflammation. IL-5 deficient mice were studied using the dextran sulphate sodium (DSS)-induced colitis model and the results compared to a congenic IL-5+/+ strain. The absence of IL-5 resulted in reduction of tissue eosinophilia (P Ͻ 0.0001) but was not reflected in differences in the severity of the disease (P Ͼ 0.5) or in the extent of tissue damage in this model of colitis. Numbers of immunoglobulin-containing cells in IL-5 deficient mice were similar to those in the IL-5+ mice. We conclude that the main role of IL-5 in DSS-induced colonic inflammation is to attract a population of eosinophils which do not appear to contribute significantly to the initiation or development of tissue damage in this model of colitis. Genes and Immunity (2000) 1, 213-218.

Tissue Eosinophilia in a Mouse Model of Colitis Is Highly Dependent on TLR2 and Independent of Mast Cells

“…14,52 Eosinophil accumulation in the mucosa is a common feature observed during DSS-induced colitis in mice. 16,17 We and others have previously shown that TLR2 signaling in response to the commensal microflora is important in limiting mucosal injury during DSS colitis. 25,26 TLR2-deficient animals have been shown to have a more severe disease development, with an extended time course and slower recovery after cessation of DSS treatment.…”

“…16,17 Mediators such as CCL5, LTB 4 , and LTC 4 have also been implicated in models of local eosinophilic inflammation and may have a role in the eosinophilic response noted in DSS colitis. 7 In other models of pathogen-induced eosinophilia, it has been shown that direct stimulation of TLR2 by M. bovis can induce an eosinophilic infiltration into the pleural cavity that is highly dependent on IL-5, CCL11, and the CCL11 receptor CCR3.…”

“…16,17 In untreated mice, there were no significant differences between TLR2 Ϫ/Ϫ and control mice in the levels of IL-5 or CCL11 in the cecum or the mid-colon (Figure 2). After DSS treatment, cecal and colonic CCL11 levels significantly increased in both groups of mice; however.…”

“…14,15 Eosinophil numbers are known to be significantly increased in the mucosa and submucosa of the colon in C57BL/6 mice after dextran sodium sulfate (DSS) treatment, a well characterized and widely used model of inducible colitis. 16,17 Moreover, this eosinophil recruitment was highly dependent on the activity of CCL11. 16,18 Toll-like receptors (TLR) are a family of innate immune pattern recognition receptors that recognize pathogenassociated molecular patterns.…”

Effects of Proteoglycan on Dextran Sulfate Sodium-Induced Experimental Colitis in Rats

“…In human UC, although the significance of eosinophil infiltration is unclear, the infiltration is significantly less marked in patients requiring surgery than in those responding to medical treatment [22]. In DSS colitis, the degree of eosinophil infiltration does not reflect the severity of the disease or the extent of tissue damage [23]. Eosinophils may act as homeostastic immune modulators and play an anti-inflammatory role, releasing aryl sulfatase B, phospholipase D, histaminase, and other chemical mediators [24][25][26][27].…”