Enteropathy cytokines

Whilst the expulsion of intestinal nematodes is absolutely Th2-mediated (Chapter 17 and below), the associated enteropathy is indistinguishable from that previously attributed to Thl-like responses. The solution to this paradox, which is addressed below, may therefore reside in the recognition of common mediators of tissue destruction, remodelling and repair, induced by both Thl and Th2 cytokine-dependent processes. 

Upon activation, mast cells release numerous mediators, including vasoactive amines, proteases, pro-inflammatory cytokines (e.g. IL-ip, IL-6, IL-18 and TNF-a) and also regulatory Th2 cytokines (e.g. IL-4, IL-10 and IL-13) (Burd et al., 1989 Gordon and Galli, 1990 Marietta el al., 1996 Toru et al., 1998 Aoki et al., 1999 Lorentz et al, 2000). Therefore, the mastocytosis in the infected mucosa represents an immunopathological rather than a protective response. Indeed, our studies have shown that expulsion of T. spiralis from TNF-Rl / or iNOS / mice was achieved in the absence of a substantial mastocytosis and subsequent amelioration of enteropathy (Lawrence etal., 1998, 2000). 

Although it appears that severe IL-4-regulated enteropathy is not required for immune expulsion of T. spiralis, it is still possible that Th2 cytokines can act in a direct fashion to create an environment unfavourable for intestinal parasites. It remains to be shown directly whether these effects are sufficient to expel parasites. Indeed, there is considerable evidence to support a variety of pathophysiological effects of IL-4 and/or TNF on the gut. These effects may be mediated by factors including cytokines and mast-cell products (e.g. leukotrienes and 5-hydroxytryptamine). 7. spiralis infections result in increased fluid and mucus secretion into the lumen as well as increased intestinal propulsive activity and more rapid intestinal transit (Castro et al, 1979 Russell, 1986 Vermillion and Collins, 1988 Vermillion et al., 1991 Weisbrodt et al, 1994 Barbara et al, 1997). The increased contractility of radial and longitudinal muscle is greater in high-... 

Garside, P., Bunce, C., Tomlinson, R.C., Nichols, B.L. and Mowat, A.M. (1993) Analysis of enteropathy induced by tumour necrosis factor alpha. Cytokine 5, 24-30. 

Guy-Grand, D., DiSanto,J.P., Henchoz, P., Malassis-Seris, M. and Vassalli, P. (1998) Small bowel enteropathy role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal. European Journal of Immunology 28, 730-744. 

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