Development and Sequels of Intestinal Inflammation in Nematode-Infected Rats: Role of Mast Cells and Capsaicin-Sensitive Afferents

Abstract

Objectives: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats. Methods: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen. In the second series, six groups of 6 rats were used to study the effects of gut extrinsic sensory neuron depletion by capsaicin. For each series, four groups of rats were infected with N. brasiliensis and two groups were not infected. Results: Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO) activity and mast cell numbers at day 12 postinfection; MPO returned to preinfection levels by day 35 while mast cell numbers remained elevated at that time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less pronounced, but MPO activity remained elevated and mast cell numbers were increased at day 35. In capsaicin-treated infected rats, the MPO increase at day 12 was augmented, and MPO was still not returned to preinfection values by day 35; in contrast, the increase of mast cell numbers at days 12 and 35 was not modified by afferent nerve depletion. Conclusion: Mast cell stabilization decreased jejunal inflammation during the acute stage (day 12), but prolonged the inflammatory process until at least day 35 postinfection. The data also confirmed the protective role of gut extrinsic sensory neurons against intestinal inflammation in a model of nematode infection and revealed that these afferent nerves do not seem crucial for the development of nematode-induced hypermastocytosis.

Mast Cell Stabilizer Ketotifen [4-(1-Methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one Fumarate] Prevents Mucosal Mast Cell Hyperplasia and Intestinal Dysmotility in Experimental Trichinella spiralis Inflammation in the Rat

“…Two main mechanisms have been suggested for the remodelation of intestinal motor patterns during inflammation: increasing sensitivity of the GI reflexes increasing activity of vagal afferents (Stead, 1992;Gay et al, 2000b;Di Giorgio et al, 2001;Torrents et al, 2002) and modifying sensitivity of the smooth muscle (Tanovic et al, 2002). Mast cells have been located in close connection to vagal afferents.…”

Effect of intestinal inflammation on capsaicin-sensitive afferents in the ileum of Schistosoma mansoni -infected mice

“…Similar results have been described by Gottwald and co-workers (1997), who observed a reduction in mucosal mast cells in the rat jejunum after capsaicin treatment in neonatal rats. Caution should be exerted, however, when generalizing these findings to other inflammatory models, because another report (Gay et al 2000) showed that neonatal capsaicin treatment had no effect on the number of mast cells in the jejunum of rats infected with Nippostrongylus brasiliensis.…”

“…All injections with capsaicin and its vehicle were performed under ether anesthesia. The effectiveness of capsaicin treatment was tested by means of the eye-wiping test, which consists of impaired chemosensitivity of corneal afferents to one drop of 1% NH 4 OH instilled to the eye (Gay et al 2000). The ileum of capsaicin-treated (n=3), vehicle-injected (n=2), and non-treated control mice (n=3) was obtained 14 days after the first injection and processed for cryosectioning or whole-mount preparations.…”

Interrelationship of feeding with immunity and parasitic infection: a review

“…Worms' toxins stimulate the production of gastrointestinal hormones, like gastrin and cholecystokinin, causing reduction in voluntary feed intake. The production of hydrochloric acid in the abdomen, except the immediate vicinity of helminths, decreases (Gay et al, 2000). Digestion and absorption of nutrients are also reduced and the endogenous nitrogen excretion elevates.…”