IL‐5 drives eosinophils from bone marrow to blood and tissues in a guinea‐pig model of visceral larva migrans syndrome

Abstract

This study was undertaken to evaluate the role of IL-5 in eosinophil migration and in the maintenance of eosinophilia in a guinea-pig model of visceral larva migrans syndrome. The results show that the infection of animals with Toxocara canis induced an early increase in serum IL-5 levels that might be essential for eosinophil differentiation and proliferation and for the development of eosinophilia. When infected guinea-pigs were treated with mAb anti-IL-5 (TRFK-5) given at the same time or 1 or 3 days after infection, there was a high percentage of reduction of eosinophil counts 18 days after infection. However, when the mAb was administered during the peak of eosinophilia, there was high inhibition in blood, no inhibition in bronchoalveolar lavage fluid (BALF) or peritoneum and an increase in eosinophil numbers in bone marrow. Thus, a basic level of IL-5 may be essential to drive eosinophils from bone marrow to blood and tissues, and for the maintenance of eosinophilia in infected animals. We may also conclude that when eosinophils have already migrated to the lungs, TRFK-5 has no power to inhibit eosinophilia, which is also under control of local lung cells producing IL-5. In this way, only one later TRFK-5 treatment may not be sufficient to modify the lung parenchyma microenvironment, since T. canis antigens had already stimulated some cell populations to produce IL-5.

Cytokines in the modulation of eosinophilia

“…In contrast to blood and BALF, the number of eosinophils in the peritoneal cavity increased significantly only at day 12 post-infection and increased progressively until day 24. The percentage of eosinophils in some animals reached 55% at the peak of infection (Faccioli et al 1996).…”

Interleukin-5 mediates peritoneal eosinophilia induced by the F1 cell wall fraction of Histoplasma capsulatum

“…More recently we have investigated the factors involved in eosinophil migration in different experimental models of eosinophilia. Using a murine model of toxocariasis, a nematode infection, we demonstrated the role of IL-5 in driving eosinophils from bone marrow to blood and tissues and in modulating IL-8 production in eosinophilic inflammation (7,8). In addition, we demonstrated that leukotrienes play a role in the leukocyte recruitment to the peritoneal cavity induced by the alkali-insoluble fraction 1 (F1), which contains mainly ß-glucan, from the cell wall of Histoplasma capsulatum, a dimorphic pathogenic fungus (9).…”

“…It has also been demonstrated that anti-IL-5 mAb treatment inhibits eosinophilia in mice infected with Toxocara canis, Nippostrongylus brasiliensis and Schistosoma mansoni (14)(15)(16). In addition, IL-5 plays an important role in mobilizing eosinophils from bone marrow to peripheral blood and in priming eosinophils to respond easily to other chemotactic stimuli such as chemokines and lipid mediators (7,17). When a low dose of IL-5 is administered intravenously, it rapidly and dramatically enhances the eosinophil accumulation induced by intradermally injected eotaxin and leukotriene B 4 (17), suggesting a link between chemoattractant factors and IL-5.…”

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

“…canis eggs were obtained according to the method of Olson and Schulz (20), modified by Faccioli et al (3). Briefly, female worms were recovered from young dogs and the eggs were removed from the uteri, washed and allowed to develop to the infective stage (L3) in shallow dishes containing 0.5% formalin at 37°C.…”

“…In general, helminthic parasites infect vertebrate hosts and typically promote a Th2-type inflammatory response that is marked by eosinophilia, high levels of immunoglobulin E (IgE) and mast cell hyperplasia (2). Studies from our laboratory have shown an accumulation of eosinophils and increased total serum IgE during the course of T. canis infection in guinea pigs (3) and Wistar rats (4). Despite the presence of elevated levels of circulating IgE during eosinophilic inflammation (5,6) and the capacity of mast cell secretory products to promote the traffic of leukocytes to the challenge sites (7,8), the relative importance of the IgE-mast cell system for the maintenance of the chronic inflammatory response to helminthic infections is controversial.…”