described by Johann Konrad Peyer (1653-1712), over a total intestinal surface of some 300 m , there are about 10 immunocytes per m or about 2 11 2 one per 6-7 enterocytes. Intra-epithelial immunocytes are mainly T lymphocytes, either (cid:0)-(cid:0) of thymic origin or (cid:0)-(cid:0) of local origin. The latter induce a Th-2 type response that is anti-inflammatory and immunosuppressive, quite important to prevent excessive stimulation due to alimentary, bacterial, viral and toxic antigens. Perdue (1999) has emphasized that a continuous cross-talk between immunocytes and enterocytes may maintain a healthy homeostasis and prevent breakdown of the mucosal barrier and inflammation. In spite of interesting hypotheses (Fiocchi, 1998, 1999; van Parijs and Abbas, 1998; Okabe, 2001; Shanahan, 2002; Ardizzone and Bianchi Porro, 2002), the etiology and pathogenesis of both ulcerative colitis and Crohn’s disease remain uncertain and it is difficult to identify the culprits that, step by step, cause the disease. Using the current paradigm of T-cell homeostasis, ulcerative colitis seems compatible with a poorly polarized Th-2 response while Crohn’s disease is characterized by an excessive Th-1 response. In other words, any alteration of the balance between pro-inflammatory (IL-1, IL-2, IFN(cid:0), TNF(cid:0)) and anti-inflammatory cytokines (IL-10, TGF-(cid:0)) appears critical (Schreiber et al., 1995), and an excessive release of IL-4, which affects the enterocytes, also appears important in ulcerative colitis (Perdue,

- 1999).

Another piece of the puzzle is represented by a more or less adequate synthesis of Hereman’s “protective vernix” i.e. A-type immunoglobulins (Ig) produced by plasma cells (B lymphocytes). IgAs have a critical role in neutralizing foreign antigens and this may limit the onset of an autoimmune process. Once this starts, the vicious circle is complicated by other cells, namely cytotoxic lymphocytes, monocytes, macrophages and granulocytes, and by the release of other inflammatory compounds such as ROS, proteinases, eicosanoids and platelet-activating factor (PAF). During the last twenty years, official medicine has made a great effort to sort out this intricate problem. Yet still today Crohn’s disease remains a serious affliction. D’Ambrosio (2000 a and b), in a open study, has shown thar RI can lead to a marked improvement of these affections. If his results could be confirmed, no patient should miss this opportunity and we ought to present a rational basis for using ozonetherapy. Table 4 shows a possible treatment scheme that could be adopted for a randomized clinical trial. Intuitively I feel that the local treatment should be combined with two-three AHTs weekly, plus a supporting therapy with antioxidants, probiotics and omega-3 PUFA. It will be important to perform at least a pilot trial and investigate whether AHT coupled to RI will be able to re-equilibrate the immune response and lead to normal mucosal metabolism. Official medicine is really struggling to find an effective treatment as critically examined by 55 Chapter 6 Hanauer and Dassopoulos (2001), who have reviewed pros and cons of as many as twenty possibilities. In Chapter 9, Section V, there is an ample discussion regarding the novel therapy with antibodies to TNF alpha.